Sterile Water for Irrigation is indicated for use as an irrigant.

{ "type": "p", "children": [], "text": "Sterile Water for Irrigation is indicated for use as an irrigant." }

The volume and/or rate of irrigation depend on the type of the procedure and the capacity or the surface area of the structure to be irrigated.

For single-dose only. Sterile Water for Irrigation is available in a flexible plastic container and a plastic pour bottle. Use the contents of the opened container immediately to minimize the potential for bacterial growth and pyrogen formation. Discard the unused contents of opened containers, as Sterile Water for Irrigation contains no antimicrobial preservative.

Adding Medications to Either the Flexible Plastic Container or the Plastic Pour Bottle

Administration Instructions for Irrigation by Gravity Using the Flexible Plastic Container

Warming

If desired, warm the flexible plastic container in overwrap to near body temperature in a water bath or fluid warmer heated to not more than 45°C.

Microwave heating of irrigation fluids is not recommended.

Administration Using the Plastic Pour Bottle

Warming

If desired, warm the plastic pour bottle in a fluid warmer to not more than 50°C for a maximum of 60 days. Discard after 60 days of warming.

Microwave heating of irrigation fluids is not recommended.

Irrigation:

{ "type": "p", "children": [], "text": "Irrigation: " }

{ "type": "", "children": [], "text": "" }

None.

{ "type": "p", "children": [], "text": "None." }

Sterile Water for Irrigation is hypotonic with an osmolarity of zero mOsmol/L. It is intended for use as irrigation fluid and not for intravenous administration or administration by other, usual parenteral routes, such as intravascular administration in general, subcutaneous administration, or intramuscular administration.

Serious adverse reactions, including cerebral or pulmonary edema, massive hemolysis, and acute renal failure can result from the hypotonicity of Sterile Water for Irrigation [see Warnings and Precautions (5.2)].

Due to the hypotonicity, absorption of Sterile Water for Irrigation can result in serious adverse reactions of hyponatremia, hypoosmolality and fluid overload, resulting in fatality or permanent morbidity. Complications include cerebral edema, encephalopathy, pulmonary edema, massive hemolysis, rhabdomyolysis, renal failure, and hyperkalemia [see Adverse Reactions (6)]. In addition, excessive volume or pressure of the irrigation fluid may also cause undue distension of body cavities and may cause tissue disruption (e.g., tears or perforation). These complications can manifest after irrigation has ended and immediate intervention may be required.

Monitor patients closely for absorption of clinically relevant amounts of fluid during and for an appropriate period after the procedure. If absorption occurs, discontinue Sterile Water for Irrigation.

Additional close monitoring during and/or after the procedure is recommended for patients at increased risk for developing complications related to hypotonicity, such as:

Avoid use of Sterile Water for Irrigation in patients with wounds where significant absorption may occur, such as procedures that require irrigation over a longer period of time or an irrigation fluid pressure that promotes absorption (e.g., transurethral resection of prostate). Sterile Water for Irrigation should only be used by clinicians familiar with the treatment of possible complications.

In contrast to other irrigation fluids containing electrolytes, Sterile Water for Irrigation is non-conductive. Therefore, when choosing the distension solution/fluid used with electrosurgery or cautery, ensure compatibility with the equipment.

The following adverse reactions have been identified during post approval use of Sterile Water for Irrigation. Because these reactions are reported voluntarily from a population of uncertain size, it is not always possible to reliably estimate their frequency or establish a causal relationship to drug exposure.

{ "type": "p", "children": [], "text": "The following adverse reactions have been identified during post approval use of Sterile Water for Irrigation. Because these reactions are reported voluntarily from a population of uncertain size, it is not always possible to reliably estimate their frequency or establish a causal relationship to drug exposure." }

Metabolism and Nutrition disorders: Hyponatremia, fluid overload, fluid absorption, electrolyte imbalance Nervous System Disorders: Cerebral edema General Disorders and Administration Site Conditions: Burning sensation (with irrigation of eyes and skin wounds) Musculoskeletal and Connective Tissue Disorders: Rhabdomyolysis (myoglobinuria) Renal and Urinary Disorders: Renal failure

{ "type": "p", "children": [], "text": "\nMetabolism and Nutrition disorders: Hyponatremia, fluid overload, fluid absorption, electrolyte imbalance\nNervous System Disorders: Cerebral edema\nGeneral Disorders and Administration Site Conditions: Burning sensation (with irrigation of eyes and skin wounds)\nMusculoskeletal and Connective Tissue Disorders: Rhabdomyolysis (myoglobinuria)\nRenal and Urinary Disorders: Renal failure\n" }

Other Adverse reactions which may occur in association with absorption of water for irrigation include:

{ "type": "p", "children": [], "text": "Other Adverse reactions which may occur in association with absorption of water for irrigation include:" }

Blood and Lymphatic System Disorders: Hemolysis (hemoglobinemia, hemoglobinuria) Metabolism and Nutrition Disorders: Hypervolemia, hypoosmolality, hyperkalemia, acid/base balance disorder Nervous System Disorders: Encephalopathy (seizure, loss of vision, lethargy, disorientation, irritability, vomiting, nausea, headache) Cardiac Disorders: Cardiac arrest, cardiac failure, bradycardia, electrocardiogram abnormal Vascular Disorders: Hypertension, postoperative hypotension Respiratory, Thoracic and Mediastinal Disorders: Respiratory arrest, respiratory failure, pulmonary edema

{ "type": "p", "children": [], "text": "\nBlood and Lymphatic System Disorders: Hemolysis (hemoglobinemia, hemoglobinuria)\nMetabolism and Nutrition Disorders: Hypervolemia, hypoosmolality, hyperkalemia, acid/base balance disorder\nNervous System Disorders: Encephalopathy (seizure, loss of vision, lethargy, disorientation, irritability, vomiting, nausea, headache)\nCardiac Disorders: Cardiac arrest, cardiac failure, bradycardia, electrocardiogram abnormal\nVascular Disorders: Hypertension, postoperative hypotension\nRespiratory, Thoracic and Mediastinal Disorders: Respiratory arrest, respiratory failure, pulmonary edema" }

Risk Summary

Appropriate administration of Sterile Water for Irrigation is not expected to cause adverse developmental outcomes. There are no available data on Sterile Water for Irrigation use in pregnant women to determine a drug-associated risk of adverse developmental outcomes. Animal reproduction studies have not been conducted with Sterile Water for Irrigation.

All pregnancies have a background risk of birth defect, loss, or other adverse outcomes. In the U.S. general population, the estimated background risk of major birth defects and miscarriage in clinically recognized pregnancies is 2 to 4% and 15 to 20% respectively.

Risk Summary

Appropriate administration of Sterile Water for Irrigation is not expected to cause harm to a breastfed infant. There are no data on the presence of Sterile Water for Irrigation in either human or animal milk, the effects on the breastfed infant or the effects on milk production. The lack of clinical data during lactation precludes a clear determination of the risk of Sterile Water for Irrigation to a breastfed infant; therefore, the developmental and health benefits of breastfeeding should be considered along with the mother’s clinical need for Sterile Water for Irrigation and any potential adverse effects on the breastfed infant from Sterile Water for Irrigation or from the underlying maternal condition.

Safety and effectiveness in pediatric patients have not been established. Pediatric patients are at higher risk compared to adults for developing encephalopathy as a complication of hyponatremia, if there is excessive absorption of Sterile Water for Irrigation [see Warnings and Precautions (5.2)].

Sterile Water for Irrigation should be used cautiously in older patients. Geriatric patients are more likely to have decreased cardiac, renal, or hepatic function, and other diseases or concomitant drug therapy.

Excessive rate, volume, pressure or duration of irrigation with hypotonic fluid can result in excessive fluid absorption and permanent morbidity or death as a result of hyponatremia, hypoosmolality and/or fluid overload. In the event of clinically relevant absorption of Sterile Water for Irrigation, immediate intervention may be required [see Warnings and Precautions (5.2)].

{ "type": "p", "children": [], "text": "Excessive rate, volume, pressure or duration of irrigation with hypotonic fluid can result in excessive fluid absorption and permanent morbidity or death as a result of hyponatremia, hypoosmolality and/or fluid overload. In the event of clinically relevant absorption of Sterile Water for Irrigation, immediate intervention may be required [see Warnings and Precautions (5.2)]." }

Sterile Water for Irrigation contains water that is sterilized and packaged for use as an irrigant. No antimicrobial agent or other substance has been added. The pH is 5.5 (5.0 to 7.0). Sterile Water for Irrigation is hypotonic with an osmolarity of zero mOsmol/L.

{ "type": "p", "children": [], "text": "Sterile Water for Irrigation contains water that is sterilized and packaged for use as an irrigant. No antimicrobial agent or other substance has been added. The pH is 5.5 (5.0 to 7.0). Sterile Water for Irrigation is hypotonic with an osmolarity of zero mOsmol/L. " }

The flexible plastic container is fabricated from a specially formulated polyvinyl chloride. The amount of water that can permeate from inside the container into the overwrap is insufficient to affect the fluid significantly. Water in contact with the plastic container may leach out certain chemical components from the plastic in very small amounts; however, biological testing was supportive of the safety of the plastic container materials.

{ "type": "p", "children": [], "text": "The flexible plastic container is fabricated from a specially formulated polyvinyl chloride. The amount of water that can permeate from inside the container into the overwrap is insufficient to affect the fluid significantly. Water in contact with the plastic container may leach out certain chemical components from the plastic in very small amounts; however, biological testing was supportive of the safety of the plastic container materials." }

The plastic pour bottle is fabricated from specially formulated polyolefin. The polyolefin is a copolymer of ethylene and propylene. The container requires no vapor barrier.

{ "type": "p", "children": [], "text": "The plastic pour bottle is fabricated from specially formulated polyolefin. The polyolefin is a copolymer of ethylene and propylene. The container requires no vapor barrier." }

Sterile Water for Irrigation is supplied in single-dose plastic pour bottles and flexible plastic containers as follows:

{ "type": "p", "children": [], "text": "Sterile Water for Irrigation is supplied in single-dose plastic pour bottles and flexible plastic containers as follows:" }

<div class="scrollingtable"><table width="100%"> <col width="27%"/> <col width="22%"/> <col width="23%"/> <col width="28%"/> <tbody class="Headless"> <tr class="First"> <td class="Botrule Lrule Rrule Toprule" valign="top"> <dl> <dt> </dt> <dd> <span class="Bold"><span class="Underline">Container</span></span> </dd> </dl> </td><td align="center" class="Botrule Lrule Rrule Toprule" valign="top"> <p class="First"> <span class="Bold"><span class="Underline">Product Codes</span></span> </p> </td><td align="center" class="Botrule Lrule Rrule Toprule" valign="top"> <p class="First"> <span class="Bold"><span class="Underline">Fill Volume (mL)</span></span> </p> </td><td align="center" class="Botrule Lrule Rrule Toprule" valign="top"> <p class="First"> <span class="Bold"><span class="Underline">NDC</span></span> </p> </td> </tr> <tr> <td align="center" class="Botrule Lrule Rrule" rowspan="4" valign="top"> <p class="First"> <span class="Bold">Plastic Pour Bottle</span> </p> </td><td align="center" class="Botrule Lrule Rrule Toprule" valign="top"> <p class="First">2F7112</p> </td><td align="center" class="Botrule Lrule Rrule Toprule" valign="top"> <p class="First">250</p> </td><td align="center" class="Botrule Lrule Rrule Toprule" valign="top"> <p class="First">0338-0004-02</p> </td> </tr> <tr> <td align="center" class="Botrule Lrule Rrule Toprule" valign="top"> <p class="First">2F7113</p> </td><td align="center" class="Botrule Lrule Rrule Toprule" valign="top"> <p class="First">500</p> </td><td align="center" class="Botrule Lrule Rrule Toprule" valign="top"> <p class="First">0338-0004-03</p> </td> </tr> <tr> <td align="center" class="Botrule Lrule Rrule Toprule" valign="top"> <p class="First">2F7114</p> </td><td align="center" class="Botrule Lrule Rrule Toprule" valign="top"> <p class="First">1000</p> </td><td align="center" class="Botrule Lrule Rrule Toprule" valign="top"> <p class="First">0338-0004-04</p> </td> </tr> <tr> <td align="center" class="Botrule Lrule Rrule Toprule" valign="top"> <p class="First">2F7115</p> </td><td align="center" class="Botrule Lrule Rrule Toprule" valign="top"> <p class="First">1500</p> </td><td align="center" class="Botrule Lrule Rrule Toprule" valign="top"> <p class="First">0338-0004-05</p> </td> </tr> <tr> <td align="center" class="Botrule Lrule Rrule" rowspan="3" valign="top"> <p class="First"> <span class="Bold">Flexible Plastic Container</span> </p> </td><td align="center" class="Botrule Lrule Rrule Toprule" valign="top"> <p class="First">2B7114</p> </td><td align="center" class="Botrule Lrule Rrule Toprule" valign="top"> <p class="First">1000</p> </td><td align="center" class="Botrule Lrule Rrule Toprule" valign="top"> <p class="First">0338-0003-44</p> </td> </tr> <tr> <td align="center" class="Botrule Lrule Rrule Toprule" valign="top"> <p class="First">2B7116</p> </td><td align="center" class="Botrule Lrule Rrule Toprule" valign="top"> <p class="First">2000</p> </td><td align="center" class="Botrule Lrule Rrule Toprule" valign="top"> <p class="First">0338-0003-46</p> </td> </tr> <tr class="Last"> <td align="center" class="Botrule Lrule Rrule Toprule" valign="top"> <p class="First">2B7117</p> </td><td align="center" class="Botrule Lrule Rrule Toprule" valign="top"> <p class="First">3000</p> </td><td align="center" class="Botrule Lrule Rrule Toprule" valign="top"> <p class="First">0338-0003-47</p> </td> </tr> </tbody> </table></div>

{ "type": "table", "children": [], "text": "<div class=\"scrollingtable\"><table width=\"100%\">\n<col width=\"27%\"/>\n<col width=\"22%\"/>\n<col width=\"23%\"/>\n<col width=\"28%\"/>\n<tbody class=\"Headless\">\n<tr class=\"First\">\n<td class=\"Botrule Lrule Rrule Toprule\" valign=\"top\">\n<dl>\n<dt> </dt>\n<dd>\n<span class=\"Bold\"><span class=\"Underline\">Container</span></span>\n</dd>\n</dl>\n</td><td align=\"center\" class=\"Botrule Lrule Rrule Toprule\" valign=\"top\">\n<p class=\"First\">\n<span class=\"Bold\"><span class=\"Underline\">Product Codes</span></span>\n</p>\n</td><td align=\"center\" class=\"Botrule Lrule Rrule Toprule\" valign=\"top\">\n<p class=\"First\">\n<span class=\"Bold\"><span class=\"Underline\">Fill Volume (mL)</span></span>\n</p>\n</td><td align=\"center\" class=\"Botrule Lrule Rrule Toprule\" valign=\"top\">\n<p class=\"First\">\n<span class=\"Bold\"><span class=\"Underline\">NDC</span></span>\n</p>\n</td>\n</tr>\n<tr>\n<td align=\"center\" class=\"Botrule Lrule Rrule\" rowspan=\"4\" valign=\"top\">\n<p class=\"First\">\n<span class=\"Bold\">Plastic Pour Bottle</span>\n</p>\n</td><td align=\"center\" class=\"Botrule Lrule Rrule Toprule\" valign=\"top\">\n<p class=\"First\">2F7112</p>\n</td><td align=\"center\" class=\"Botrule Lrule Rrule Toprule\" valign=\"top\">\n<p class=\"First\">250</p>\n</td><td align=\"center\" class=\"Botrule Lrule Rrule Toprule\" valign=\"top\">\n<p class=\"First\">0338-0004-02</p>\n</td>\n</tr>\n<tr>\n<td align=\"center\" class=\"Botrule Lrule Rrule Toprule\" valign=\"top\">\n<p class=\"First\">2F7113</p>\n</td><td align=\"center\" class=\"Botrule Lrule Rrule Toprule\" valign=\"top\">\n<p class=\"First\">500</p>\n</td><td align=\"center\" class=\"Botrule Lrule Rrule Toprule\" valign=\"top\">\n<p class=\"First\">0338-0004-03</p>\n</td>\n</tr>\n<tr>\n<td align=\"center\" class=\"Botrule Lrule Rrule Toprule\" valign=\"top\">\n<p class=\"First\">2F7114</p>\n</td><td align=\"center\" class=\"Botrule Lrule Rrule Toprule\" valign=\"top\">\n<p class=\"First\">1000</p>\n</td><td align=\"center\" class=\"Botrule Lrule Rrule Toprule\" valign=\"top\">\n<p class=\"First\">0338-0004-04</p>\n</td>\n</tr>\n<tr>\n<td align=\"center\" class=\"Botrule Lrule Rrule Toprule\" valign=\"top\">\n<p class=\"First\">2F7115</p>\n</td><td align=\"center\" class=\"Botrule Lrule Rrule Toprule\" valign=\"top\">\n<p class=\"First\">1500</p>\n</td><td align=\"center\" class=\"Botrule Lrule Rrule Toprule\" valign=\"top\">\n<p class=\"First\">0338-0004-05</p>\n</td>\n</tr>\n<tr>\n<td align=\"center\" class=\"Botrule Lrule Rrule\" rowspan=\"3\" valign=\"top\">\n<p class=\"First\">\n<span class=\"Bold\">Flexible Plastic Container</span>\n</p>\n</td><td align=\"center\" class=\"Botrule Lrule Rrule Toprule\" valign=\"top\">\n<p class=\"First\">2B7114</p>\n</td><td align=\"center\" class=\"Botrule Lrule Rrule Toprule\" valign=\"top\">\n<p class=\"First\">1000</p>\n</td><td align=\"center\" class=\"Botrule Lrule Rrule Toprule\" valign=\"top\">\n<p class=\"First\">0338-0003-44</p>\n</td>\n</tr>\n<tr>\n<td align=\"center\" class=\"Botrule Lrule Rrule Toprule\" valign=\"top\">\n<p class=\"First\">2B7116</p>\n</td><td align=\"center\" class=\"Botrule Lrule Rrule Toprule\" valign=\"top\">\n<p class=\"First\">2000</p>\n</td><td align=\"center\" class=\"Botrule Lrule Rrule Toprule\" valign=\"top\">\n<p class=\"First\">0338-0003-46</p>\n</td>\n</tr>\n<tr class=\"Last\">\n<td align=\"center\" class=\"Botrule Lrule Rrule Toprule\" valign=\"top\">\n<p class=\"First\">2B7117</p>\n</td><td align=\"center\" class=\"Botrule Lrule Rrule Toprule\" valign=\"top\">\n<p class=\"First\">3000</p>\n</td><td align=\"center\" class=\"Botrule Lrule Rrule Toprule\" valign=\"top\">\n<p class=\"First\">0338-0003-47</p>\n</td>\n</tr>\n</tbody>\n</table></div>" }

Storage

{ "type": "p", "children": [], "text": "\nStorage\n" }

Exposure of pharmaceutical products to heat should be minimized. Avoid excessive heat.

{ "type": "p", "children": [], "text": "\nExposure of pharmaceutical products to heat should be minimized. Avoid excessive heat. " }

Store at room temperature (25°C): brief exposure up to 40°C does not adversely affect the product.

{ "type": "p", "children": [], "text": "\nStore at room temperature (25°C): brief exposure up to 40°C does not adversely affect the product." }

Inform patients, caregivers, or home healthcare providers of the following risks of Sterile Water for Irrigation:

{ "type": "p", "children": [], "text": "Inform patients, caregivers, or home healthcare providers of the following risks of Sterile Water for Irrigation: " }

{ "type": "", "children": [], "text": "" }

Baxter Healthcare CorporationDeerfield, IL 60015 USA

{ "type": "p", "children": [], "text": "Baxter Healthcare CorporationDeerfield, IL 60015 USA" }

Printed in USA07-19-77-916

{ "type": "p", "children": [], "text": "Printed in USA07-19-77-916" }

Baxter is a registered trademark of Baxter International Inc.

{ "type": "p", "children": [], "text": "Baxter is a registered trademark of Baxter International Inc." }

{ "type": "", "children": [], "text": "" }

2F7114NDC 0338-0004-04

{ "type": "p", "children": [], "text": "\n2F7114NDC 0338-0004-04\n" }

1000 mL

{ "type": "p", "children": [], "text": "\n1000 mL\n" }

Baxter Logo

{ "type": "p", "children": [], "text": "\nBaxter Logo\n" }

Not for Injection

{ "type": "p", "children": [], "text": "\nNot for Injection\n" }

For Irrigation Only

{ "type": "p", "children": [], "text": "\nFor Irrigation Only\n" }

Sterile Water forIrrigation USP

{ "type": "p", "children": [], "text": "\nSterile Water forIrrigation USP\n" }

Prepared by distillation. No antimicrobial agentor other substance has been added. pH 5.5 (5.0 to 7.0). Osmolarity 0 mOsmol/L (calc.). Sterile, nonpyrogenic. Pour Bottle. Warning: This solution is not isotonic and is hemolytic. Dosage and Administration: As directed by a physician. Cautions: Warm in oven to not more than 50ºC for a maximum of 60 days. Discard after 60 days of warming. Do not use unless solution is clear and seal is intact. Discard unused portion. Rx only. Recommended storage: Room temperature (25ºC). Avoid excessive heat.

{ "type": "p", "children": [], "text": "Prepared by distillation. No antimicrobial agentor other substance has been added. pH 5.5 (5.0 to 7.0). Osmolarity 0 mOsmol/L (calc.). Sterile, nonpyrogenic. Pour Bottle. Warning: This solution is not isotonic and is hemolytic. Dosage and Administration: As directed by a physician. Cautions: Warm in oven to not more than 50ºC for a maximum of 60 days. Discard after 60 days of warming. Do not use unless solution is clear and seal is intact. Discard unused portion. Rx only. Recommended storage: Room temperature (25ºC). Avoid excessive heat." }

PL 325 Plastic

{ "type": "p", "children": [], "text": "PL 325 Plastic" }

Baxter Healthcare Corporation Deerfield, IL 60015 USAMade in USA

{ "type": "p", "children": [], "text": "\nBaxter Healthcare Corporation\nDeerfield, IL 60015 USAMade in USA" }

LOTEXP

{ "type": "p", "children": [], "text": "LOTEXP" }

FPO(91)0709000246Bar Code

{ "type": "p", "children": [], "text": "FPO(91)0709000246Bar Code" }

07-09-00-0246

{ "type": "p", "children": [], "text": "07-09-00-0246" }

Bar Code Position Only*303380004041

{ "type": "p", "children": [], "text": "Bar Code Position Only*303380004041" }

LOTEXP2000 mLNOT FOR INJECTION2B7116NDC 0338-0003-46STERILE WATER For Irrigation USP

{ "type": "p", "children": [], "text": "\nLOTEXP2000 mLNOT FOR INJECTION2B7116NDC 0338-0003-46STERILE WATER For Irrigation USP\n" }

For irrigation only Prepared by distillationNo antimicrobial agent or other substance has been addedpH 5.5 (5.0 TO 7.0). Osmolarity 0 mOsmol/L (calc) SterileNonpyrogenic Single dose container

{ "type": "p", "children": [], "text": "For irrigation only Prepared by distillationNo antimicrobial agent or other substance has been addedpH 5.5 (5.0 TO 7.0). Osmolarity 0 mOsmol/L (calc) SterileNonpyrogenic Single dose container" }

Do not use unless fluid is clear Discard unused portion

{ "type": "p", "children": [], "text": "Do not use unless fluid is clear Discard unused portion " }

Cautions This fluid is not isotonic and is hemolyticSqueeze and inspect inner bag which maintains productsterility Discard if leaks are found Rx Only Store unit inmoisture barrier overwrap at room temperature (25ºC) untilReady to use Avoid excessive heat See insert

{ "type": "p", "children": [], "text": "Cautions This fluid is not isotonic and is hemolyticSqueeze and inspect inner bag which maintains productsterility Discard if leaks are found Rx Only Store unit inmoisture barrier overwrap at room temperature (25ºC) untilReady to use Avoid excessive heat See insert" }

Sterile WaterH20For Irrigation USP

{ "type": "p", "children": [], "text": "\nSterile WaterH20For Irrigation USP\n" }

UROMATIC container

{ "type": "p", "children": [], "text": "UROMATIC container" }

Baxter Logo Baxter Healthcare CorporationDeerfield IL 60015 USA

{ "type": "p", "children": [], "text": "\nBaxter Logo\nBaxter Healthcare CorporationDeerfield IL 60015 USA" }

Made in USA

{ "type": "p", "children": [], "text": "Made in USA" }

PL 146 Plastic

{ "type": "p", "children": [], "text": "PL 146 Plastic" }

Baxter UROMATIC andPL 146 are trademarks ofBaxter International Inc

{ "type": "p", "children": [], "text": "Baxter UROMATIC andPL 146 are trademarks ofBaxter International Inc" }

For product information1-800-933-0303

{ "type": "p", "children": [], "text": "For product information1-800-933-0303" }

18001600140012001000800600400200

{ "type": "p", "children": [], "text": "18001600140012001000800600400200" }

IC-GREEN is indicated for fluorescence imaging of vessels (micro- and macro- vasculature), blood flow and tissue perfusion before, during and after vascular, gastrointestinal, organ transplant, plastic, micro- and reconstructive surgeries, including general minimally invasive surgical procedures in adults and pediatric patients aged 1 month and older.

IC-GREEN is indicated for fluorescence imaging of extrahepatic biliary ducts in adults and pediatric patients aged 12 years and older.

IC-GREEN is indicated for fluorescence imaging of lymph nodes and delineation of lymphatic vessels during lymphatic mapping in adults with cervical and uterine cancer for which this procedure is a component of intraoperative management.

IC-GREEN is indicated for use in ophthalmic angiography in adults and pediatric patients.

Dosing

Adults:

The recommended dose of IC-GREEN for a single image sequence for visualization of vessels, blood flow and tissue perfusion in adults is 1.25 mg to 5 mg administered intravenously as 0.5 mL to 2 mL of a 2.5 mg/mL solution.

For visualization of perfusion in extremities through the skin in adults, the recommended dose is 3.75 mg to 10 mg administered intravenously as 1.5 mL to 4 mL of a 2.5 mg/mL solution.

Immediately flush with a 10 mL bolus of 0.9% Sodium Chloride Injection.

Pediatric patients aged 1 month and older:

The recommended dose of IC-GREEN for a single image sequence for visualization of vessels, blood flow and tissue perfusion in pediatric patients aged 1 month and older is 1.25 mg to 5 mg administered intravenously as 0.5 mL to 2 mL of a 2.5 mg/mL solution. Lower doses may be administered in younger patients and in those with lower body weight. Adjust the amount and type of flush to avoid volume and/or sodium overload.

In both adults and pediatric patients aged 1 month and older, additional doses may be administered to obtain imaging sequences during the procedure. Do not exceed the maximum total dose of 2 mg/kg.

Administration

Prior to the imaging procedure, draw up the desired dose of IC-GREEN solution into appropriate syringes and prepare a 10 mL syringe of 0.9% Sodium Chloride Injection.

Administer via a central or peripheral venous line using a three-way stopcock attached to an injection port on the infusion line. Inject the prepared IC-GREEN into the line as a tight bolus. Immediately switch the access on the stopcock and inject the prepared flush.

Imaging Instructions

IC-GREEN may be used with an FDA-authorized imaging device that is intended to be used with indocyanine green for fluorescence imaging of vessels, blood flow and tissue perfusion.

A fluorescence response should be visible in blood vessels within 5 seconds to 15 seconds after injection.

Dosing and Administration

The recommended dose of IC-GREEN for visualization of extrahepatic biliary ducts in adults and pediatric patients aged 12 years and older is 2.5 mg administered intravenously as 1 mL of a 2.5 mg/mL solution at least 45 minutes prior to surgery.

Additional doses may be administered to obtain imaging sequences during the procedure.

Do not exceed a total dose of 2 mg/kg.

Imaging Instructions

IC-GREEN may be used with an FDA-authorized imaging device that is intended to be used with indocyanine green for fluorescence imaging of extrahepatic biliary ducts.

Fluorescence is visible in the biliary tree within 45 minutes after injection.

Dosing and Administration

The recommended dose of IC-GREEN for lymphatic mapping of cervical and uterine cancer in adults is 5 mg administered interstitially as four 1 mL injections of a 1.25 mg/mL solution into the cervix, at the 3 o’ clock and the 9 o’clock positions with a superficial (1 mm to 3 mm) and a deep (1 cm to 3 cm) injection at each position.

Imaging Instructions

IC-GREEN may be used with an FDA-authorized imaging device that is intended to be used with indocyanine green for fluorescence imaging of lymph nodes and delineation of lymphatic vessels during lymphatic mapping of cervical and uterine cancer.

Fluorescent lymphatic vessels and lymph nodes should begin to be visible within 1 minute after injection.

Dosing and Administration

Doses up to 40 mg IC-GREEN in 2 mL of Sterile Water for Injection depending on the imaging equipment and technique used should be administered intravenously and immediately followed by a 5 mL bolus of 0.9% Sodium Chloride Injection. The antecubital vein can be used for IC-GREEN administration.

General

Visualization of Vessels, Blood Flow, Tissue Perfusion and Extrahepatic Biliary Ducts

Dissolve 25 mg of IC-GREEN with 10 mL Sterile Water for Injection to form a concentration of 2.5 mg/mL indocyanine green.

Lymphatic Mapping of Cervical and Uterine Cancer

Dissolve 25 mg of IC-GREEN with 20 mL Sterile Water for Injection to form a concentration of 1.25 mg/mL indocyanine green.

Ophthalmic Angiography

Dissolve doses up to 40 mg of IC-GREEN with 2 mL Sterile Water for Injection.

For injection: 25 mg of indocyanine green as a sterile, lyophilized, green powder for reconstitution provided in a 25 mL single-patient-use vial.

{ "type": "p", "children": [], "text": "For injection: 25 mg of indocyanine green as a sterile, lyophilized, green powder for reconstitution provided in a 25 mL single-patient-use vial." }

IC-GREEN is contraindicated in patients with a history of hypersensitivity to indocyanine green. Reactions have included anaphylaxis [see Warnings and Precautions (5.1)].

{ "type": "p", "children": [], "text": "IC-GREEN is contraindicated in patients with a history of hypersensitivity to indocyanine green. Reactions have included anaphylaxis [see Warnings and Precautions (5.1)]." }

Hypersensitivity reactions including anaphylaxis, urticaria and deaths due to anaphylaxis have been reported following intravenous administration of IC-GREEN [see Adverse Reactions (6)].

IC-GREEN is contraindicated in patients with a history of hypersensitivity to indocyanine green [see Contraindications (4)]. Always have cardiopulmonary resuscitation personnel and equipment readily available and monitor all patients for hypersensitivity reactions.

Because IC-GREEN contains sodium iodide, the iodine-binding capacity of thyroid tissue may be reduced for at least one week following administration [see Drug Interactions (7)].

The following clinically significant adverse reactions are described elsewhere in the labeling:

{ "type": "p", "children": [], "text": "The following clinically significant adverse reactions are described elsewhere in the labeling:" }

{ "type": "", "children": [], "text": "" }

The following adverse reactions have been identified during post-approval use of IC-GREEN. Because these reactions are reported voluntarily from a population of uncertain size, it is not always possible to reliably estimate their frequency or establish a causal relationship to drug exposure.

{ "type": "p", "children": [], "text": "The following adverse reactions have been identified during post-approval use of IC-GREEN. Because these reactions are reported voluntarily from a population of uncertain size, it is not always possible to reliably estimate their frequency or establish a causal relationship to drug exposure." }

Immune System Disorders: Anaphylaxis, urticaria

{ "type": "p", "children": [], "text": "\nImmune System Disorders: Anaphylaxis, urticaria" }

Interference with Thyroid Radioactive Iodine Uptake Studies

{ "type": "p", "children": [], "text": "\nInterference with Thyroid Radioactive Iodine Uptake Studies\n" }

Because IC-GREEN contains sodium iodide, the iodine-binding capacity of thyroid tissue may be reduced for at least one week following administration. Do not perform radioactive iodine uptake studies for at least one week following administration of IC-GREEN.

{ "type": "p", "children": [], "text": "Because IC-GREEN contains sodium iodide, the iodine-binding capacity of thyroid tissue may be reduced for at least one week following administration. Do not perform radioactive iodine uptake studies for at least one week following administration of IC-GREEN." }

There are no adequate and well-controlled studies of IC-GREEN in pregnant women. Available data from a very small number of scientific literature studies with indocyanine green use in pregnant women over several decades have not reported any drug associated risks for major birth defects, miscarriage, or adverse maternal or fetal outcomes. Data from one small study in which indocyanine green was administered intravenously to pregnant women during labor suggest there is no placental transfer of the drug. Animal reproduction studies have not been conducted with indocyanine green.

All pregnancies have a background risk of birth defects, loss, or other adverse outcomes. In the U.S. general population, the estimated background risk of major birth defects and miscarriage in clinically recognized pregnancies is 2 to 4% and 15 to 20%, respectively.

Seventeen cases of indocyanine green use in lactating women have been reported in the scientific literature with no adverse events observed in the breastfed infant. However, there are no data on the presence of indocyanine green in human milk or the effects on milk production. Therefore, the developmental and health benefits of breastfeeding should be considered along with the mother's clinical need for IC-GREEN and any potential adverse effects on the breastfed infant from IC-GREEN or from the underlying maternal condition.

Use of IC-GREEN for visualization of vessels, blood flow and tissue perfusion has been established in pediatric patients aged 1 month and older. Pediatric use is supported by published data in 49 pediatric patients who received indocyanine green for assessment of blood flow and tissue perfusion in cardiovascular, vascular, and plastic, micro- and reconstructive surgical procedures, and by clinical trials in adults. No overall differences in safety or effectiveness have been observed between pediatric patients and adults. The dose range was similar to the effective dose range in adults [see Dosage and Administration (2.1)]. The use of IC-GREEN for visualization of vessels, blood flow and tissue perfusion has not been established in pediatric patients aged less than 1 month.

Use of IC-GREEN for visualization of extrahepatic biliary ducts has been established in pediatric patients aged 12 years and older. Pediatric use is supported by clinical trials in adults in addition to clinical use in pediatric patients. No overall differences in safety or effectiveness have been observed between pediatric patients and adults. The dose range was similar to the effective dose range in adults [see Dosage and Administration (2.2)]. The use of IC-GREEN for visualization of extrahepatic biliary ducts has not been established in pediatric patients aged less than 12 years.

Use of IC-GREEN for visualization of lymph nodes and lymphatic vessels during lymphatic mapping for cervical and uterine cancer have not been established in pediatric patients.

Use of IC-GREEN for ophthalmic angiography has been established in pediatric patients. Pediatric use is supported by evidence from the published literature.

Of the total number of patients in clinical studies of indocyanine green for injection for visualization of vessels, blood flow and tissue perfusion, 7% were 65 and over, while 1% were 75 and over. Of the total number of patients in clinical studies of indocyanine green for injection for visualization of lymph nodes and lymphatic vessels during lymphatic mapping of cervical and uterine cancer, 9% were 65 and over, while 2% were 75 and over. Clinical studies of indocyanine green for injection for visualization of extrahepatic biliary ducts did not include sufficient numbers of patients aged 65 and over to determine whether they respond differently from younger patients.

No overall differences in safety or effectiveness were observed between these patients and younger patients, and other reported clinical experience has not identified differences in responses between elderly and younger patients. In general, dose selection for an elderly patient should be cautious, usually starting at the low end of the dosing range, reflecting the greater frequency of decreased hepatic, renal or cardiac function, and of concomitant disease or other drug therapy.

IC-GREEN (indocyanine green for injection) is an optical imaging agent for intravenous or interstitial use.

{ "type": "p", "children": [], "text": "IC-GREEN (indocyanine green for injection) is an optical imaging agent for intravenous or interstitial use. " }

Each vial contains 25 mg of indocyanine green with not more than 5% sodium iodide as a sterile, lyophilized, green powder. IC-GREEN has a pH of 5.5-7.5 when reconstituted with Sterile Water for Injection, USP.

{ "type": "p", "children": [], "text": "Each vial contains 25 mg of indocyanine green with not more than 5% sodium iodide as a sterile, lyophilized, green powder. IC-GREEN has a pH of 5.5-7.5 when reconstituted with Sterile Water for Injection, USP." }

The chemical name for Indocyanine Green is 1 HBenz[e]indolium, 2-[7-[1,3-dihydro-1,1-dimethyl-3-(4- sulfobutyl)-2H-benz[e]indol-2-ylidene]-1,3,5-heptatrienyl]-1,1-dimethyl-3-(4-sulfobutyl)-, hydroxide, inner salt, sodium salt.

{ "type": "p", "children": [], "text": "The chemical name for Indocyanine Green is 1 HBenz[e]indolium, 2-[7-[1,3-dihydro-1,1-dimethyl-3-(4- sulfobutyl)-2H-benz[e]indol-2-ylidene]-1,3,5-heptatrienyl]-1,1-dimethyl-3-(4-sulfobutyl)-, hydroxide, inner salt, sodium salt." }

Molecular Formula: C43H47N2NaO6S2; Molecular Mass: 774.96 g/mol, with the following structural formula:

{ "type": "p", "children": [], "text": "Molecular Formula: C43H47N2NaO6S2; Molecular Mass: 774.96 g/mol, with the following structural formula:" }

Indocyanine green has a peak spectral absorption at 805 nm in blood.

{ "type": "p", "children": [], "text": "Indocyanine green has a peak spectral absorption at 805 nm in blood." }

When bound to proteins in plasma or in lymph fluid, indocyanine green absorbs light in the near-infrared region with peak absorption at 805 nm and emits fluorescence (light) at a slightly longer wavelength, with peak emission at 830 nm. Fluorescence imaging devices provide external energy as near infrared light for indocyanine green to absorb, resulting in excitation of the indocyanine green, and the emitted light (fluorescence) is transferred from the field of view to an image on a monitor. These optical properties of indocyanine green are utilized in fluorescence imaging of the micro- and macro-vasculature, blood flow and tissue perfusion, the extrahepatic biliary ducts, and for lymphatic mapping of lymph nodes and lymphatic vessels.

There are no pharmacodynamic data.

Distribution

Following intravenous injection, indocyanine green binds to plasma proteins (98%) and is largely confined to the intravascular compartment. Indocyanine green undergoes no significant extrahepatic or enterohepatic circulation; simultaneous arterial and venous blood estimations have shown negligible renal, peripheral, lung or cerebro-spinal uptake of the dye. After biliary obstruction, the dye appears in the hepatic lymph, independently of the bile, suggesting that the biliary mucosa is sufficiently intact to prevent diffusion of the dye, though allowing diffusion of bilirubin.

Following interstitial injection, indocyanine green binds to proteins in lymph fluid and the interstitial space, is taken up by the lymphatic vessels, and drains to the lymph nodes.

Since excessive dye extravasation does not take place in the highly fenestrated choroidal vasculature, IC-GREEN is useful in both absorption and fluorescence infrared angiography of the choroidal vasculature when using appropriate filters and film in a fundus camera.

Elimination

Indocyanine green is taken up from the plasma almost exclusively by the hepatic parenchymal cells and is secreted entirely into the bile.

No studies have been performed to evaluate the potential for carcinogenicity, mutagenicity, or impairment of fertility by indocyanine green.

The effectiveness of IC-GREEN for fluorescence imaging of lymph nodes and delineation of lymphatic vessels during lymphatic mapping in adults with cervical and uterine cancer has been established based on a study of another formulation of indocyanine green for injection. Below is a description of the FILM Study (NCT 02209532).

The study was a randomized, prospective, multi-center, open-label study in patients with early stage uterine or cervical cancer and no known regional nodal or metastatic disease by standard clinical evaluation. Indocyanine green and a blue dye comparator were injected into the cervix of patients at the beginning of the operative procedure.

A total of 176 patients were randomized to receive either indocyanine green followed by blue dye or blue dye followed by indocyanine green. A total of four 1 mL injections of a 1.25 mg/ml solution of indocyanine green for a total dose of 5 mg were administered interstitially into the cervix at the 3 o'clock and 9 o'clock positions with a superficial (1 mm to 3 mm) and a deep (1 cm to 3 cm) injection at each position.

Lymphatic mapping was performed intraoperatively using a fluorescence imaging device and standard light, followed by excision of tissues identified by indocyanine green, blue dye, or the surgeon's visual and palpation examination. The resected tissues were evaluated by histopathology to confirm presence of lymph nodes. The efficacy of indocyanine green in the detection of lymphatic vessels and lymph nodes during lymphatic mapping procedures was determined by the number of histology-confirmed lymph nodes detected by indocyanine green and/or the blue dye comparator.

The mean age of the 176 patients was 63 years (range: 31 to 88 years); distribution by race and ethnicity was 79% White, 4% Black or African American, 3% Asian, 13% Hispanic/Latino and 1% other.

Table 1 shows the distribution of resected, confirmed lymph nodes detected by indocyanine green or blue dye in the modified intent-to-treat population (mlTT). Among the confirmed lymph nodes identified, 93% were identified using indocyanine green, and 43% were identified using blue dye, a difference of 50% [95% confidence interval 39% to 60%].

<div class="scrollingtable"><table cellpadding="3.6pt" width="100%"> <caption> <span>Table 1: Distribution of Resected, Confirmed Lymph Nodes Detected by Indocyanine Green or Blue Dye (BD)</span> </caption> <col width="16%"/> <col width="10%"/> <col width="16%"/> <col width="14%"/> <col width="15%"/> <col width="13%"/> <col width="14%"/> <tbody class="Headless"> <tr class="First"> <td class="Botrule Rrule" valign="middle"> <p class="First"> <span class="Bold">Analysis Population</span> </p> </td><td class="Botrule Lrule Rrule" valign="middle"> <p class="First"> <span class="Bold">Nodes (n)</span> </p> </td><td class="Botrule Lrule Rrule" valign="middle"> <p class="First"> <span class="Bold">All Lymph Nodes Detected with Indocyanine Green</span> </p> </td><td class="Botrule Lrule Rrule" valign="middle"> <p class="First"> <span class="Bold">All Lymph Nodes Detected with BD</span> </p> </td><td class="Botrule Lrule Rrule" valign="middle"> <p class="First"> <span class="Bold">Lymph Nodes Detected with Indocyanine Green Only</span> </p> </td><td class="Botrule Lrule Rrule" valign="middle"> <p class="First"> <span class="Bold">Lymph Nodes Detected with BD Only</span> </p> </td><td class="Botrule Lrule" valign="middle"> <p class="First"> <span class="Bold">Lymph Nodes Detected with Neither</span> </p> </td> </tr> <tr class="Last"> <td class="Rrule Toprule" valign="middle"> <p class="First">mlTT</p> </td><td class="Lrule Rrule Toprule" valign="middle"> <p class="First">513</p> </td><td class="Lrule Rrule Toprule" valign="middle"> <p class="First">(476/513)<br/>93%</p> </td><td class="Lrule Rrule Toprule" valign="middle"> <p class="First">(220/513)<br/>43%</p> </td><td class="Lrule Rrule Toprule" valign="middle"> <p class="First">(262/513)<br/>51%</p> </td><td class="Lrule Rrule Toprule" valign="middle"> <p class="First">(6/513)<br/>1%</p> </td><td class="Lrule Toprule" valign="middle"> <p class="First">(31/513)<br/>6%</p> </td> </tr> </tbody> </table></div>

Table 2 shows the number of patients with at least one resected, confirmed lymph node and the number of patients with at least one bilateral lymph node pair detected by indocyanine green or blue dye. With indocyanine green, approximately 97% of patients had at least one resected, confirmed lymph node detected and 73% had at least one bilateral lymph node pair detected, compared with 68% and 28%, respectively, with blue dye (p-values for each analysis <0.0001).

<div class="scrollingtable"><table cellpadding="3.6pt" width="100%"> <caption> <span>Table 2: Distribution of Patients with at Least One Confirmed Unilateral Lymph Node/ Bilateral Pair Detected by Indocyanine Green or Blue Dye (BD)</span> </caption> <col width="16%"/> <col width="10%"/> <col width="16%"/> <col width="15%"/> <col width="14%"/> <col width="14%"/> <col width="14%"/> <tfoot> <tr class="First Last"> <td align="left" colspan="7" valign="top">*: patients with at least one resected confirmed lymph node detected unilaterally<br/>**: patients with at least one resected confirmed lymph node detected bilaterally</td> </tr> </tfoot> <tbody class="Headless"> <tr class="First"> <td class="Botrule Rrule" valign="middle"> <p class="First"> <span class="Bold">Analysis Population</span> </p> </td><td class="Botrule Lrule Rrule" valign="middle"> <p class="First"> <span class="Bold">Patients (n)</span> </p> </td><td class="Botrule Lrule Rrule" valign="middle"> <p class="First"> <span class="Bold">Patients with All Lymph Nodes Detected with Indocyanine Green</span> </p> </td><td class="Botrule Lrule Rrule" valign="middle"> <p class="First"> <span class="Bold">Patients with All Lymph Nodes Detected with BD</span> </p> </td><td class="Botrule Lrule Rrule" valign="middle"> <p class="First"> <span class="Bold">Patients with Lymph Nodes Detected with Indocyanine Green only</span> </p> </td><td class="Botrule Lrule Rrule" valign="middle"> <p class="First"> <span class="Bold">Patients with Lymph Nodes Detected with BD only</span> </p> </td><td class="Botrule Lrule" valign="middle"> <p class="First"> <span class="Bold">Patients with Lymph Nodes Detected with Neither</span> </p> </td> </tr> <tr> <td class="Botrule Rrule" valign="middle"> <p class="First">mlTT Unilateral*</p> </td><td class="Lrule Rrule Toprule" valign="bottom"> <p class="First">172</p> </td><td class="Botrule Lrule Rrule Toprule" valign="middle"> <p class="First">(167/172)<br/>97%</p> </td><td class="Botrule Lrule Rrule Toprule" valign="middle"> <p class="First">(118/172) <br/>68%</p> </td><td class="Botrule Lrule Rrule Toprule" valign="middle"> <p class="First">(51/172)<br/>30%</p> </td><td class="Botrule Lrule Rrule Toprule" valign="middle"> <p class="First">(2/172)<br/>1%</p> </td><td class="Botrule Lrule Toprule" valign="middle"> <p class="First">(3/172)<br/>3%</p> </td> </tr> <tr class="Last"> <td class="Rrule Toprule" valign="middle"> <p class="First">mlTT Bilateral**</p> </td><td valign="middle"></td><td class="Lrule Rrule Toprule" valign="middle"> <p class="First">(126/172)<br/>73%</p> </td><td class="Lrule Rrule Toprule" valign="middle"> <p class="First">(49/172)<br/>28%</p> </td><td class="Lrule Rrule Toprule" valign="middle"> <p class="First">(79/172)<br/>46%</p> </td><td class="Lrule Rrule Toprule" valign="middle"> <p class="First">(2/172)<br/>1%</p> </td><td class="Lrule Toprule" valign="middle"> <p class="First">(44/172) <br/>26%</p> </td> </tr> </tbody> </table></div>

How Supplied

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IC-GREEN (indocyanine green for injection) is supplied as a kit (NDC 70100-825-02) containing the following:

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Storage and Handling

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Store at 20°C to 25°C (68°F to 77°F).

{ "type": "p", "children": [], "text": "Store at 20°C to 25°C (68°F to 77°F)." }

Hypersensitivity Reactions

{ "type": "p", "children": [], "text": "\nHypersensitivity Reactions\n" }

Advise patients to seek medical attention for reactions following injection of IC-GREEN such as difficulty breathing, swollen tongue or throat, skin reactions including hives, itching and flushed or pale skin, low blood pressure, a weak and rapid pulse and other symptoms or signs of an anaphylactic reaction [see Warnings and Precautions (5.1)].

{ "type": "p", "children": [], "text": "Advise patients to seek medical attention for reactions following injection of IC-GREEN such as difficulty breathing, swollen tongue or throat, skin reactions including hives, itching and flushed or pale skin, low blood pressure, a weak and rapid pulse and other symptoms or signs of an anaphylactic reaction [see Warnings and Precautions (5.1)]." }

Manufactured by:Patheon Italia S.p.A.20900 Monza (MB), ITALY

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or

{ "type": "p", "children": [], "text": "or" }

LYOCONTRACT GmbH38871 Ilsenburg, GERMANY

{ "type": "p", "children": [], "text": "LYOCONTRACT GmbH38871 Ilsenburg, GERMANY" }

Distributed by:Diagnostic Green LLCFarmington Hills, Ml 48331

{ "type": "p", "children": [], "text": "Distributed by:Diagnostic Green LLCFarmington Hills, Ml 48331 " }

Sterile Water for injection, USP is manufactured by:Fresenius Kabi USA, LLCGrand Island, NY 14072

{ "type": "p", "children": [], "text": "Sterile Water for injection, USP is manufactured by:Fresenius Kabi USA, LLCGrand Island, NY 14072 " }

or

{ "type": "p", "children": [], "text": "or" }

Hospira, Inc.Rocky Mount, NC 27804

{ "type": "p", "children": [], "text": "Hospira, Inc.Rocky Mount, NC 27804 " }

or

{ "type": "p", "children": [], "text": "or" }

Hikma Pharmaceuticals USA Inc.Berkeley Heights, NJ 07922

{ "type": "p", "children": [], "text": "Hikma Pharmaceuticals USA Inc.Berkeley Heights, NJ 07922" }

51047

{ "type": "p", "children": [], "text": "51047" }

{ "type": "", "children": [], "text": "" }

NDC 70100-725-01          Rx only    Sterile

{ "type": "p", "children": [], "text": "NDC 70100-725-01          Rx only    Sterile" }

IC-GREEN® (indocyanine greenfor injection)

{ "type": "p", "children": [], "text": "\nIC-GREEN®\n\n(indocyanine greenfor injection)" }

25 mg/Vial

{ "type": "p", "children": [], "text": "\n25 mg/Vial\n" }

Single-Patient-UseFor Intravenous or Interstitial Use After reconstitution, use within 6 hours.

{ "type": "p", "children": [], "text": "\nSingle-Patient-UseFor Intravenous or Interstitial Use\nAfter reconstitution, use within 6 hours." }

Distributed by: Diagnostic Green LLC

{ "type": "p", "children": [], "text": "Distributed by: Diagnostic Green LLC" }

51045          12/2024

{ "type": "p", "children": [], "text": "51045          12/2024" }

Lot No.Exp.:

{ "type": "p", "children": [], "text": "Lot No.Exp.:" }

{ "type": "", "children": [], "text": "" }

10 mL   Single-dose

{ "type": "p", "children": [], "text": "\n10 mL   Single-dose" }

Sterile Water for Injection, USP

{ "type": "p", "children": [], "text": "\nSterile Water\nfor Injection, USP" }

FOR DRUG DILUENT USE

{ "type": "p", "children": [], "text": "FOR DRUG DILUENT USE" }

Rx only               NDC 0409-4887-17

{ "type": "p", "children": [], "text": "Rx only               NDC 0409-4887-17" }

Contains no antimicrobial or other addedsubstance. Sterile, nonpyrogenic. Do not giveintravenously unless rendered nearly isotonic.

{ "type": "p", "children": [], "text": "\nContains no antimicrobial or other addedsubstance. Sterile, nonpyrogenic. Do not giveintravenously unless rendered nearly isotonic." }

Hospira, Inc.              RL-4428Lake Forest, IL 60045 USA

{ "type": "p", "children": [], "text": "Hospira, Inc.              RL-4428Lake Forest, IL 60045 USA" }

{ "type": "", "children": [], "text": "" }

NDC 70100-825-02          Rx Only - Sterile

{ "type": "p", "children": [], "text": "NDC 70100-825-02          Rx Only - Sterile" }

IC-GREEN® (indocyanine green for injection)

{ "type": "p", "children": [], "text": "\nIC-GREEN®\n(indocyanine green for injection)" }

25 mg/Vial

{ "type": "p", "children": [], "text": "\n25 mg/Vial\n" }

Single-Patient-Use     For Intravenous or Interstitial Use

{ "type": "p", "children": [], "text": "\nSingle-Patient-Use     For Intravenous or Interstitial Use\n" }

Distributed by: Diagnostic Green LLC

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Back Panel

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NDC 70100-825-02           Rx Only - Sterile

{ "type": "p", "children": [], "text": "NDC 70100-825-02           Rx Only - Sterile" }

Recommended Dosage and ReconstitutionInstructions: See Prescribing Information Use within 6 hours after reconsituition.

{ "type": "p", "children": [], "text": "\nRecommended Dosage and ReconstitutionInstructions: See Prescribing Information\nUse within 6 hours after reconsituition." }

STORAGE: Store at 20° to 25° C (68° to 77°F) KIT CONTAINS: • Six vials of IC-GREEN (25 mg each)• Six Sterile Water for Injection (10 mL each)

{ "type": "p", "children": [], "text": "\nSTORAGE: Store at 20° to 25° C (68° to 77°F)\nKIT CONTAINS:\n• Six vials of IC-GREEN (25 mg each)• Six Sterile Water for Injection (10 mL each)" }

IC-GREEN® (indocyanine green for injection)

{ "type": "p", "children": [], "text": "\nIC-GREEN®\n(indocyanine green for injection)" }

25 mg/Vial

{ "type": "p", "children": [], "text": "\n25 mg/Vial\n" }

Single-Patient-Use     For Intravenous or Interstitial Use

{ "type": "p", "children": [], "text": "\nSingle-Patient-Use     For Intravenous or Interstitial Use\n" }

Side Panel

{ "type": "p", "children": [], "text": "\nSide Panel\n" }

IC-GREEN® (indocyanine green for injection)

{ "type": "p", "children": [], "text": "\nIC-GREEN®\n(indocyanine green for injection)\n" }

Distributed by: Diagnostic Green LLC Farmington Hills MI 48331 USA

{ "type": "p", "children": [], "text": "Distributed by:\nDiagnostic Green LLC\nFarmington Hills MI 48331 USA" }

Manufactured by: Patheon Italia S.p.A. 20052 Monza (Milano) ITALYor Lyocontract GmbH 38871 IlsenburgGERMANY

{ "type": "p", "children": [], "text": "Manufactured by:\nPatheon Italia S.p.A.\n20052 Monza (Milano) ITALYor\nLyocontract GmbH\n38871 IlsenburgGERMANY" }

Sterile Water Manufactured by:Hospira, Inc.Rocky Mount, NC 27804orFresenius Kabi USA, LLCGrand Island, NY 14072orHikma PharmaceuticalsUSA Inc.Berkeley Heights, NJ 07922

{ "type": "p", "children": [], "text": "Sterile Water Manufactured by:Hospira, Inc.Rocky Mount, NC 27804orFresenius Kabi USA, LLCGrand Island, NY 14072orHikma PharmaceuticalsUSA Inc.Berkeley Heights, NJ 07922" }

04/2025

{ "type": "p", "children": [], "text": "04/2025" }

JYNNEOS is a vaccine indicated for prevention of smallpox and mpox disease in adults 18 years of age and older determined to be at high risk for smallpox or monkeypox infection.

{ "type": "p", "children": [], "text": "JYNNEOS is a vaccine indicated for prevention of smallpox and mpox disease in adults 18 years of age and older determined to be at high risk for smallpox or monkeypox infection." }

JYNNEOS is supplied in two presentations, a one vial-presentation and a two-vial presentation.

One-Vial Presentation

The one-vial presentation contains JYNNEOS in a single vial with a yellow cap and does not require reconstitution before use.

Two-Vial Presentation

The two-vial presentation includes a vial with a yellow cap containing Lyophilized Antigen Component (Vial A) and a vial with a blue cap containing Diluent Component (Vial B). The Lyophilized Antigen Component must be reconstituted with the Diluent Component to form JYNNEOS prior to administration.

Instructions for JYNNEOS One-Vial Presentation

Allow the vaccine to thaw and reach room temperature before use. Once thawed, the vaccine may be kept at +2°C to +8°C (+36°F to +46°F) for 4 weeks. Protect from light during storage.

Do not refreeze.

Swirl the vial gently before use for at least 30 seconds. Withdraw a dose of 0.5 mL into a sterile syringe for injection.

Reconstitution Instructions for JYNNEOS Two-Vial Presentation

Reconstitute the Lyophilized Antigen Component (Vial A, yellow cap) with Diluent Component (Vial B, blue cap) to form JYNNEOS, as described in Figure 1 through Figure 4.

After reconstitution, the vaccine may be stored at +2°C to +8°C (+36°F to +46°F) for 12 hours. Protect from light during storage.

JYNNEOS is a milky, light yellow to pale white colored suspension. Parenteral drug products should be inspected visually for particulate matter and discoloration prior to administration, whenever solution and container permit. If either of these conditions exist, the vaccine should not be administered.

Administer each 0.5 mL dose of JYNNEOS subcutaneously.

Administer two doses (0.5 mL each) of JYNNEOS 4 weeks apart.

JYNNEOS is an injectable suspension. A single dose is 0.5 mL.

{ "type": "p", "children": [], "text": "JYNNEOS is an injectable suspension. A single dose is 0.5 mL." }

Appropriate medical treatment must be available to manage possible anaphylactic reactions following administration of JYNNEOS.

Persons who experienced a severe allergic reaction following a previous dose of JYNNEOS or following exposure to any component of JYNNEOS may be at increased risk for severe allergic reactions after JYNNEOS. The risk for a severe allergic reaction should be weighed against the risk for disease due to smallpox or mpox.

Syncope (fainting) has been reported following vaccination with JYNNEOS. Procedures should be in place to avoid injury from fainting.

Immunocompromised persons, including those receiving immunosuppressive therapy, may have a diminished immune response to JYNNEOS.

Vaccination with JYNNEOS may not protect all recipients.

Because clinical trials are conducted under widely varying conditions, adverse reaction rates observed in the clinical trials of a vaccine cannot be directly compared with rates in the clinical trials of another vaccine, and may not reflect the rates observed in practice. There is the possibility that broad use of JYNNEOS could reveal adverse reactions not observed in clinical trials.

Safety data accrued with the one-vial presentation is relevant to the two-vial presentation because each contains the same live, attenuated, non-replicating orthopoxvirus and is manufactured using a similar process.

The overall clinical trial program included 23 studies (14 studies with the one-vial presentation, 7 studies with the two-vial presentation, and 2 studies with both one-vial and two-vial presentations) and a total of 8,988 participants 18 through 80 years of age who received at least 1 dose of JYNNEOS (8,222 smallpox vaccine-naïve and 766 smallpox vaccine-experienced participants). Of the 8,988 participants, 6,459 participants received the one-vial presentation and 2,529 participants received the two-vial presentation.

Solicited Adverse Reactions

Solicited Adverse Reactions in Smallpox Vaccine-Naïve Individuals:

The safety of JYNNEOS one-vial presentation in smallpox vaccine-naïve participants was evaluated in Study 1 [1], a randomized, double-blind, placebo-controlled study conducted in the US in which vaccinia-naïve adults ages 18 to 40 years received either two doses of JYNNEOS (N=3,003), or two injections of Tris-Buffered Saline (placebo, N=1,002) four weeks apart.

In the total study population, the mean age was 28 years; 47.9% of the participants were men; 77.4% were white/Caucasian, 17.8% black/African American, 1.9% Asian, 0.5% American Indian/Alaska Native, 0.4% Native Hawaiian/Other Pacific, 1.9% other racial groups; and 11.4% of participants were of Hispanic/Latino ethnicity. The demographic distribution was similar in the JYNNEOS and placebo groups.

In Study 1, participants were monitored for local and systemic adverse reactions using diary cards for an 8-day period starting on the day of each vaccination. The frequencies of solicited local and systemic adverse reactions following any dose of JYNNEOS are presented in Table 1.

<div class="scrollingtable"><table cellpadding="3.6pt" width="100%"> <caption> <span>Table 1: Percentages of Participants with Solicited Local Injection Site Reactions and Systemic Adverse Reactions within 8 Days of Administration of Any Dose of JYNNEOS in Adults 18 to 40 Years of Age, Study 1<span class="Sup">x</span></span> </caption> <col width="35%"/> <col width="30%"/> <col width="35%"/> <thead> <tr class="First Last"> <th align="left" class="Botrule Lrule Rrule Toprule" valign="top"><span class="Bold">Reaction</span></th><th align="center" class="Botrule Lrule Rrule Toprule" valign="top"><span class="Bold">JYNNEOS</span> <br/> <span class="Bold">N=2943</span> <br/> <span class="Bold">%</span></th><th align="center" class="Botrule Lrule Rrule Toprule" valign="top"><span class="Bold">Placebo</span> <br/> <span class="Bold">N=980 </span> <br/> <span class="Bold">%</span></th> </tr> </thead> <tfoot> <tr class="First Last"> <td align="left" colspan="3" valign="top"><span class="Sup">x</span>   NCT01144637<br/> <span class="Sup">a</span>   Grade 3 pain defined as spontaneously painful<br/> <span class="Sup">b</span>   Grade 3 itching, muscle pain, headache, fatigue, nausea and chills defined as preventing routine daily activities<br/> <span class="Sup">c</span>   Fever defined as oral temperature ≥ 100.4°F (≥ 38°C), Grade ≥ 3 fever defined as ≥ 102.2°F (≥ 39.0°C)<br/>N: Number of participants in the specified treatment group</td> </tr> </tfoot> <tbody> <tr class="First"> <td class="Botrule Lrule Rrule" valign="top"> <p class="First"> <span class="Bold">Local (Injection site)</span> </p> </td><td align="center" class="Botrule Lrule Rrule Toprule" valign="top"> <p class="First"> <span class="Bold">--</span> </p> </td><td align="center" class="Botrule Lrule Rrule Toprule" valign="top"> <p class="First"> <span class="Bold">--</span> </p> </td> </tr> <tr> <td class="Botrule Lrule Rrule" valign="top"> <p class="First">Pain</p> </td><td align="center" class="Botrule Lrule Rrule Toprule" valign="top"> <p class="First">84.9</p> </td><td align="center" class="Botrule Lrule Rrule Toprule" valign="top"> <p class="First">19.1</p> </td> </tr> <tr> <td class="Botrule Lrule Rrule" valign="top"> <p class="First">Pain, Grade 3<span class="Sup">a</span> </p> </td><td align="center" class="Botrule Lrule Rrule Toprule" valign="top"> <p class="First">7.4</p> </td><td align="center" class="Botrule Lrule Rrule Toprule" valign="top"> <p class="First">1.0</p> </td> </tr> <tr> <td class="Botrule Lrule Rrule" valign="top"> <p class="First">Redness</p> </td><td align="center" class="Botrule Lrule Rrule Toprule" valign="top"> <p class="First">60.8</p> </td><td align="center" class="Botrule Lrule Rrule Toprule" valign="top"> <p class="First">17.7</p> </td> </tr> <tr> <td class="Botrule Lrule Rrule" valign="top"> <p class="First">Redness ≥ 100 mm</p> </td><td align="center" class="Botrule Lrule Rrule Toprule" valign="top"> <p class="First">1.5</p> </td><td align="center" class="Botrule Lrule Rrule Toprule" valign="top"> <p class="First">0.0</p> </td> </tr> <tr> <td class="Botrule Lrule Rrule" valign="top"> <p class="First">Swelling</p> </td><td align="center" class="Botrule Lrule Rrule Toprule" valign="top"> <p class="First">51.6</p> </td><td align="center" class="Botrule Lrule Rrule Toprule" valign="top"> <p class="First">5.6</p> </td> </tr> <tr> <td class="Botrule Lrule Rrule" valign="top"> <p class="First">Swelling ≥ 100 mm</p> </td><td align="center" class="Botrule Lrule Rrule Toprule" valign="top"> <p class="First">0.8</p> </td><td align="center" class="Botrule Lrule Rrule Toprule" valign="top"> <p class="First">0.0</p> </td> </tr> <tr> <td class="Botrule Lrule Rrule" valign="top"> <p class="First">Induration</p> </td><td align="center" class="Botrule Lrule Rrule Toprule" valign="top"> <p class="First">45.4</p> </td><td align="center" class="Botrule Lrule Rrule Toprule" valign="top"> <p class="First">4.6</p> </td> </tr> <tr> <td class="Botrule Lrule Rrule" valign="top"> <p class="First">Induration ≥ 100 mm</p> </td><td align="center" class="Botrule Lrule Rrule Toprule" valign="top"> <p class="First">0.3</p> </td><td align="center" class="Botrule Lrule Rrule Toprule" valign="top"> <p class="First">0.0</p> </td> </tr> <tr> <td class="Botrule Lrule Rrule" valign="top"> <p class="First">Itching</p> </td><td align="center" class="Botrule Lrule Rrule Toprule" valign="top"> <p class="First">43.1</p> </td><td align="center" class="Botrule Lrule Rrule Toprule" valign="top"> <p class="First">11.7</p> </td> </tr> <tr> <td class="Botrule Lrule Rrule" valign="top"> <p class="First">Itching, Grade 3<span class="Sup">b</span> </p> </td><td align="center" class="Botrule Lrule Rrule Toprule" valign="top"> <p class="First">1.6</p> </td><td align="center" class="Botrule Lrule Rrule Toprule" valign="top"> <p class="First">0.2</p> </td> </tr> <tr> <td class="Botrule Lrule Rrule" valign="top"> <p class="First"> <span class="Bold">Systemic </span> </p> </td><td align="center" class="Botrule Lrule Rrule Toprule" valign="top"> <p class="First"> <span class="Bold">--</span> </p> </td><td align="center" class="Botrule Lrule Rrule Toprule" valign="top"> <p class="First"> <span class="Bold">--</span> </p> </td> </tr> <tr> <td class="Botrule Lrule Rrule" valign="top"> <p class="First">Muscle Pain</p> </td><td align="center" class="Botrule Lrule Rrule Toprule" valign="top"> <p class="First">42.8</p> </td><td align="center" class="Botrule Lrule Rrule Toprule" valign="top"> <p class="First">17.6</p> </td> </tr> <tr> <td class="Botrule Lrule Rrule" valign="top"> <p class="First">Muscle Pain, Grade 3<span class="Sup">b</span> </p> </td><td align="center" class="Botrule Lrule Rrule Toprule" valign="top"> <p class="First">2.6</p> </td><td align="center" class="Botrule Lrule Rrule Toprule" valign="top"> <p class="First">0.7</p> </td> </tr> <tr> <td class="Botrule Lrule Rrule" valign="top"> <p class="First">Headache</p> </td><td align="center" class="Botrule Lrule Rrule Toprule" valign="top"> <p class="First">34.8</p> </td><td align="center" class="Botrule Lrule Rrule Toprule" valign="top"> <p class="First">25.6</p> </td> </tr> <tr> <td class="Botrule Lrule Rrule" valign="top"> <p class="First">Headache, Grade 3<span class="Sup">b</span> </p> </td><td align="center" class="Botrule Lrule Rrule Toprule" valign="top"> <p class="First">2.4</p> </td><td align="center" class="Botrule Lrule Rrule Toprule" valign="top"> <p class="First">2.1</p> </td> </tr> <tr> <td class="Botrule Lrule Rrule" valign="top"> <p class="First">Fatigue</p> </td><td align="center" class="Botrule Lrule Rrule Toprule" valign="top"> <p class="First">30.4</p> </td><td align="center" class="Botrule Lrule Rrule Toprule" valign="top"> <p class="First">20.5</p> </td> </tr> <tr> <td class="Botrule Lrule Rrule" valign="top"> <p class="First">Fatigue, Grade 3<span class="Sup">b</span> </p> </td><td align="center" class="Botrule Lrule Rrule Toprule" valign="top"> <p class="First">3.0</p> </td><td align="center" class="Botrule Lrule Rrule Toprule" valign="top"> <p class="First">1.3</p> </td> </tr> <tr> <td class="Botrule Lrule Rrule" valign="top"> <p class="First">Nausea</p> </td><td align="center" class="Botrule Lrule Rrule Toprule" valign="top"> <p class="First">17.3</p> </td><td align="center" class="Botrule Lrule Rrule Toprule" valign="top"> <p class="First">13.1</p> </td> </tr> <tr> <td class="Botrule Lrule Rrule" valign="top"> <p class="First">Nausea, Grade 3<span class="Sup">b</span> </p> </td><td align="center" class="Botrule Lrule Rrule Toprule" valign="top"> <p class="First">1.5</p> </td><td align="center" class="Botrule Lrule Rrule Toprule" valign="top"> <p class="First">1.2</p> </td> </tr> <tr> <td class="Botrule Lrule Rrule" valign="top"> <p class="First">Chills</p> </td><td align="center" class="Botrule Lrule Rrule Toprule" valign="top"> <p class="First">10.4</p> </td><td align="center" class="Botrule Lrule Rrule Toprule" valign="top"> <p class="First">5.8</p> </td> </tr> <tr> <td class="Botrule Lrule Rrule" valign="top"> <p class="First">Chills, Grade 3<span class="Sup">b</span> </p> </td><td align="center" class="Botrule Lrule Rrule Toprule" valign="top"> <p class="First">1.0</p> </td><td align="center" class="Botrule Lrule Rrule Toprule" valign="top"> <p class="First">0.3</p> </td> </tr> <tr> <td class="Botrule Lrule Rrule" valign="top"> <p class="First">Fever<span class="Sup">c</span> </p> </td><td align="center" class="Botrule Lrule Rrule Toprule" valign="top"> <p class="First">1.7</p> </td><td align="center" class="Botrule Lrule Rrule Toprule" valign="top"> <p class="First">0.9</p> </td> </tr> <tr class="Last"> <td class="Botrule Lrule Rrule Toprule" valign="top"> <p class="First">Fever, Grade ≥ 3<span class="Sup">c</span> </p> </td><td align="center" class="Botrule Lrule Rrule Toprule" valign="top"> <p class="First">0.2</p> </td><td align="center" class="Botrule Lrule Rrule Toprule" valign="top"> <p class="First">0.0</p> </td> </tr> </tbody> </table></div>

In Study 1, the majority of solicited local and systemic adverse reactions reported with JYNNEOS had a median duration of 1 to 6 days. In general, there were similar proportions of participants reporting solicited local or systemic reactions of any severity after Dose 2 of JYNNEOS compared with Dose 1, with the exception of injection site pain, which was more commonly reported following Dose 1 (79.3%) than Dose 2 (69.9%).

The two presentations of JYNNEOS (one-vial and two-vial) were compared in Study 2 [2], a randomized, double-blind, multicenter study conducted in the US in which vaccinia-naïve adults ages 18 to 55 years received two doses of either two-vial presentation (N=325) or one-vial presentation (N=327) JYNNEOS four weeks apart.

The mean age was approximately 28 years for both study groups; 46.5% of the participants were men; 74.7% were White/Caucasian, 22.3% Black/African American, 0.8% Oriental/Asian, 0.2% American Indian/Alaska Native, 0.3% Native Hawaiian/ Pacific Islander, 1.5% multiple racial groups, and 0.3% other racial groups; and 29.2% of participants were of Hispanic/Latino ethnicity. The demographic distribution was similar in the two JYNNEOS treatment groups.

In Study 2, participants were monitored for local and systemic adverse reactions for an 8-day period starting on the day of each vaccination. The frequencies of solicited local and systemic adverse reactions following any dose of JYNNEOS are presented in Table 2.

<div class="scrollingtable"><table class="Noautorules" width="100%"> <caption> <span>Table 2: Percentages of Participants with Solicited Local Injection Site Reactions and Systemic Adverse Reactions, Within 7 Days of Administration of Any dose of JYNNEOS in Adults 18 through 40 Years of Age (Full Analysis Set), Study 2<span class="Sup">x</span></span> </caption> <col width="33%"/> <col width="33%"/> <col width="33%"/> <tfoot> <tr> <td align="left" colspan="3" valign="top"><span class="Sup">x</span>   NCT01668537<br/> <span class="Sup">a</span>   Grade 3 pain defined as spontaneously painful/prevention of normal activity.<br/> <span class="Sup">b</span>   Grade 3 itching defined as preventing routine daily activities.<br/> <span class="Sup">c</span>   Grade 3 muscle pain, headache, fatigue, nausea and chills defined as severe; preventing routine daily activities<br/> <span class="Sup">d</span>   Fever defined as oral temperature ≥ 100.4°F (≥ 38°C), Grade ≥ 3 fever defined as ≥ 102.2°F (≥ 39.0°C)<br/>N: Number of participants in the specified treatment group</td> </tr> </tfoot> <tbody class="Headless"> <tr> <td class="Botrule Lrule Rrule Toprule" valign="top"> <p class="First"> <span class="Bold">Reaction</span> </p> </td><td align="center" class="Botrule Lrule Rrule Toprule" valign="top"> <p class="First"> <span class="Bold">JYNNEOS One-vial</span> </p> <p> <span class="Bold">Presentation</span> </p> <p> <span class="Bold">N=322</span> </p> <p> <span class="Bold">%</span> </p> </td><td align="center" class="Botrule Lrule Rrule Toprule" valign="top"> <p class="First"> <span class="Bold">JYNNEOS Two-vial</span> </p> <p> <span class="Bold">Presentation</span> </p> <p> <span class="Bold">N=321</span> </p> <p> <span class="Bold">%</span> </p> </td> </tr> <tr> <td class="Botrule Lrule Rrule" valign="top"> <p class="First"> <span class="Bold">Any Local (Injection site)</span> </p> </td><td align="center" class="Botrule Lrule Rrule Toprule" valign="top"> <p class="First"> <span class="Bold">93.2</span> </p> </td><td align="center" class="Botrule Lrule Rrule Toprule" valign="top"> <p class="First"> <span class="Bold">94.1</span> </p> </td> </tr> <tr> <td class="Botrule Lrule Rrule" valign="top"> <p class="First"> <span class="Bold">            Local (Injection site) ≥ Grade 3</span> </p> </td><td align="center" class="Botrule Lrule Rrule Toprule" valign="top"> <p class="First"> <span class="Bold">13.0</span> </p> </td><td align="center" class="Botrule Lrule Rrule Toprule" valign="top"> <p class="First"> <span class="Bold">24.0</span> </p> </td> </tr> <tr> <td class="Botrule Lrule Rrule" valign="top"> <p class="First">Pain</p> </td><td align="center" class="Botrule Lrule Rrule Toprule" valign="top"> <p class="First">85.1</p> </td><td align="center" class="Botrule Lrule Rrule Toprule" valign="top"> <p class="First">90.3</p> </td> </tr> <tr> <td class="Botrule Lrule Rrule" valign="top"> <p class="First"> <span class="Bold">            </span>Pain, Grade 3<span class="Sup">a</span> </p> </td><td align="center" class="Botrule Lrule Rrule Toprule" valign="top"> <p class="First">6.8</p> </td><td align="center" class="Botrule Lrule Rrule Toprule" valign="top"> <p class="First">10.9</p> </td> </tr> <tr> <td class="Botrule Lrule Rrule" valign="top"> <p class="First">Redness</p> </td><td align="center" class="Botrule Lrule Rrule Toprule" valign="top"> <p class="First">76.7</p> </td><td align="center" class="Botrule Lrule Rrule Toprule" valign="top"> <p class="First">79.4</p> </td> </tr> <tr> <td class="Botrule Lrule Rrule" valign="top"> <p class="First"> <span class="Bold">            </span>Redness ≥ 100 mm</p> </td><td align="center" class="Botrule Lrule Rrule Toprule" valign="top"> <p class="First">5.0</p> </td><td align="center" class="Botrule Lrule Rrule Toprule" valign="top"> <p class="First">14.6</p> </td> </tr> <tr> <td class="Botrule Lrule Rrule" valign="top"> <p class="First">Swelling</p> </td><td align="center" class="Botrule Lrule Rrule Toprule" valign="top"> <p class="First">65.2</p> </td><td align="center" class="Botrule Lrule Rrule Toprule" valign="top"> <p class="First">69.5</p> </td> </tr> <tr> <td class="Botrule Lrule Rrule" valign="top"> <p class="First"> <span class="Bold">            </span>Swelling≥ 100 mm</p> </td><td align="center" class="Botrule Lrule Rrule Toprule" valign="top"> <p class="First">3.1</p> </td><td align="center" class="Botrule Lrule Rrule Toprule" valign="top"> <p class="First">7.2</p> </td> </tr> <tr> <td class="Botrule Lrule Rrule" valign="top"> <p class="First">Induration</p> </td><td align="center" class="Botrule Lrule Rrule Toprule" valign="top"> <p class="First">65.5</p> </td><td align="center" class="Botrule Lrule Rrule Toprule" valign="top"> <p class="First">66.4</p> </td> </tr> <tr> <td class="Botrule Lrule Rrule" valign="top"> <p class="First"> <span class="Bold">            </span>Induration≥ 100 mm</p> </td><td align="center" class="Botrule Lrule Rrule Toprule" valign="top"> <p class="First">1.6</p> </td><td align="center" class="Botrule Lrule Rrule Toprule" valign="top"> <p class="First">1.9</p> </td> </tr> <tr> <td class="Botrule Lrule Rrule" valign="top"> <p class="First">Itching</p> </td><td align="center" class="Botrule Lrule Rrule Toprule" valign="top"> <p class="First">55.0</p> </td><td align="center" class="Botrule Lrule Rrule Toprule" valign="top"> <p class="First">58.9</p> </td> </tr> <tr> <td class="Botrule Lrule Rrule" valign="top"> <p class="First"> <span class="Bold">            </span>Itching, Grade 3<span class="Sup">b</span> </p> </td><td align="center" class="Botrule Lrule Rrule Toprule" valign="top"> <p class="First">2.2</p> </td><td align="center" class="Botrule Lrule Rrule Toprule" valign="top"> <p class="First">3.4</p> </td> </tr> <tr> <td class="Botrule Lrule Rrule" valign="top"> <p class="First"> <span class="Bold">Any Systemic</span> </p> </td><td align="center" class="Botrule Lrule Rrule Toprule" valign="top"> <p class="First"> <span class="Bold">56.5</span> </p> </td><td align="center" class="Botrule Lrule Rrule Toprule" valign="top"> <p class="First"> <span class="Bold">57.6</span> </p> </td> </tr> <tr> <td class="Botrule Lrule Rrule" valign="top"> <p class="First"> <span class="Bold">            Systemic ≥ Grade 3</span> </p> </td><td align="center" class="Botrule Lrule Rrule Toprule" valign="top"> <p class="First"> <span class="Bold">5.9</span> </p> </td><td align="center" class="Botrule Lrule Rrule Toprule" valign="top"> <p class="First"> <span class="Bold">5.9</span> </p> </td> </tr> <tr> <td class="Botrule Lrule Rrule" valign="top"> <p class="First">Headache</p> </td><td align="center" class="Botrule Lrule Rrule Toprule" valign="top"> <p class="First">38.8</p> </td><td align="center" class="Botrule Lrule Rrule Toprule" valign="top"> <p class="First">34.9</p> </td> </tr> <tr> <td class="Botrule Lrule Rrule" valign="top"> <p class="First"> <span class="Bold">            </span>Headache, Grade 3<span class="Sup">c</span> </p> </td><td align="center" class="Botrule Lrule Rrule Toprule" valign="top"> <p class="First">2.5</p> </td><td align="center" class="Botrule Lrule Rrule Toprule" valign="top"> <p class="First">2.2</p> </td> </tr> <tr> <td class="Botrule Lrule Rrule" valign="top"> <p class="First">Fatigue</p> </td><td align="center" class="Botrule Lrule Rrule Toprule" valign="top"> <p class="First">35.1</p> </td><td align="center" class="Botrule Lrule Rrule Toprule" valign="top"> <p class="First">31.8</p> </td> </tr> <tr> <td class="Botrule Lrule Rrule" valign="top"> <p class="First"> <span class="Bold">            </span>Fatigue, Grade 3<span class="Sup">c</span> </p> </td><td align="center" class="Botrule Lrule Rrule Toprule" valign="top"> <p class="First">4.7</p> </td><td align="center" class="Botrule Lrule Rrule Toprule" valign="top"> <p class="First">2.8</p> </td> </tr> <tr> <td class="Botrule Lrule Rrule" valign="top"> <p class="First">Muscle Pain</p> </td><td align="center" class="Botrule Lrule Rrule Toprule" valign="top"> <p class="First">21.1</p> </td><td align="center" class="Botrule Lrule Rrule Toprule" valign="top"> <p class="First">18.4</p> </td> </tr> <tr> <td class="Botrule Lrule Rrule" valign="top"> <p class="First"> <span class="Bold">            </span>Muscle Pain, Grade 3<span class="Sup">c</span> </p> </td><td align="center" class="Botrule Lrule Rrule Toprule" valign="top"> <p class="First">0.3</p> </td><td align="center" class="Botrule Lrule Rrule Toprule" valign="top"> <p class="First">1.6</p> </td> </tr> <tr> <td class="Botrule Lrule Rrule" valign="top"> <p class="First">Nausea</p> </td><td align="center" class="Botrule Lrule Rrule Toprule" valign="top"> <p class="First">17.7</p> </td><td align="center" class="Botrule Lrule Rrule Toprule" valign="top"> <p class="First">15.9</p> </td> </tr> <tr> <td class="Botrule Lrule Rrule" valign="top"> <p class="First"> <span class="Bold">            </span>Nausea, Grade 3<span class="Sup">c</span> </p> </td><td align="center" class="Botrule Lrule Rrule Toprule" valign="top"> <p class="First">1.2</p> </td><td align="center" class="Botrule Lrule Rrule Toprule" valign="top"> <p class="First">0.6</p> </td> </tr> <tr> <td class="Botrule Lrule Rrule" valign="top"> <p class="First">Chills</p> </td><td align="center" class="Botrule Lrule Rrule Toprule" valign="top"> <p class="First">11.8</p> </td><td align="center" class="Botrule Lrule Rrule Toprule" valign="top"> <p class="First">10.9</p> </td> </tr> <tr> <td class="Botrule Lrule Rrule" valign="top"> <p class="First"> <span class="Bold">            </span>Chills, Grade 3<span class="Sup">c</span> </p> </td><td align="center" class="Botrule Lrule Rrule Toprule" valign="top"> <p class="First">0.6</p> </td><td align="center" class="Botrule Lrule Rrule Toprule" valign="top"> <p class="First">1.6</p> </td> </tr> <tr> <td class="Botrule Lrule Rrule" valign="top"> <p class="First">Fever<span class="Sup">d</span> </p> </td><td align="center" class="Botrule Lrule Rrule Toprule" valign="top"> <p class="First">7.1</p> </td><td align="center" class="Botrule Lrule Rrule Toprule" valign="top"> <p class="First">10.3</p> </td> </tr> <tr> <td class="Botrule Lrule Rrule Toprule" valign="top"> <p class="First"> <span class="Bold">            </span>Fever, Grade ≥ 3<span class="Sup">d</span> </p> </td><td align="center" class="Botrule Lrule Rrule Toprule" valign="top"> <p class="First">0.9</p> </td><td align="center" class="Botrule Lrule Rrule Toprule" valign="top"> <p class="First">0.6</p> </td> </tr> </tbody> </table></div>

In Study 2, solicited systemic adverse reactions reported with both presentations had a similar median duration of 1 to 3 days. Solicited local adverse reactions reported with both presentations had a similar median duration of 4 to 6 days, except for injection site induration. The median duration of injection site induration was 11 days for the one-vial presentation and 14 days for the two-vial presentation.

Solicited Adverse Reactions in Persons Previously Vaccinated with a Smallpox Vaccine:

Three studies (Study 3, Study 4, and Study 5 [3-5]) conducted in the US and Germany evaluated the safety of JYNNEOS one-vial presentation in 409 persons previously vaccinated with a smallpox vaccine who received one or two doses of JYNNEOS (mean age 39 years, range 20-80 years; 59% women; 98.8% white/Caucasian; 0.7% Asian; 0.5% black/African American). Participants were monitored for local and systemic adverse reactions using diary cards for an 8-day period starting on the day of each vaccination. Across all three studies, solicited local adverse reactions reported following any dose of JYNNEOS were redness (80.9%), pain (79.5%), induration (70.4%), swelling (67.2%), and itching (32.0%) at the injection site; solicited systemic adverse reactions reported following any dose of JYNNEOS were fatigue (33.5%), headache (27.6%), muscle pain (21.5%), nausea (9.8%), chills (0.7%), and fever (0.5%).

Solicited Adverse Reactions in HIV-infected Individuals:

The safety of JYNNEOS one-vial presentation in HIV-infected participants was evaluated in Study 6 [6], an open label trial conducted in the US that included 351 HIV-infected smallpox vaccine-naïve participants, 131 HIV-infected participants who previously received smallpox vaccine, 88 non-HIV-infected smallpox vaccine-naïve participants and 9 non-HIV-infected participants who had previously received a smallpox vaccine. The demographic distribution (race, ethnicity, and sex) of HIV-infected smallpox vaccine-naïve participants and those who had previously received smallpox vaccine were similar and overall were 17.0% women; 45.8% white/Caucasian; 0.4% Asian; 33.2% black/African American; 19.0% Hispanic/Latino ethnicity; the HIV-infected smallpox vaccine-naïve group tended to be younger (mean age 37 years) compared to those who had previously received a smallpox vaccine (mean age 45 years). Participants had CD4 counts ≥ 200 and ≤ 750 cells/μL at study entry.

Solicited local and systemic adverse reactions were reported at similar or lower frequencies in HIV-infected smallpox vaccine-naïve participants as compared to those seen in non-HIV-infected smallpox vaccine-naive participants in this study.

In HIV-infected participants with previous smallpox vaccine exposure, fever and chills were reported in 1.5% and 8.4% of participants respectively. Frequencies of other solicited local and systemic adverse reactions in this population were similar to those reported in Studies 3-5 in non-HIV-infected participants who had previously received smallpox vaccination.

The safety of JYNNEOS two-vial presentation in HIV-infected participants was evaluated in Study 7 [7], an open label trial conducted in the US that included 30 HIV-infected smallpox vaccine-naïve participants, 61 HIV-infected participants who previously received smallpox vaccine, 30 non-HIV-infected smallpox vaccine-naïve participants, and 30 non-HIV-infected participants who had previously received a smallpox vaccine. The demographic distribution (race, ethnicity, and sex) of HIV-infected smallpox vaccine-naïve participants and those who had previously received smallpox vaccine were similar. Overall for HIV-infected participants, 29.7% of participants were women; 58.2% were white/Caucasian; 40.7% black/African American; 1.1% other race; Hispanic/Latino ethnicity was not reported; the HIV-infected smallpox vaccine-naïve group tended to be younger (mean age approximately 31 years) compared to those who had previously received a smallpox vaccine (mean age approximately 43 years). Participants had CD4 counts > 350 cells/μL at study entry.

Solicited local and systemic adverse reactions were reported at similar or lower frequencies in HIV-infected smallpox vaccine-naïve participants as compared to those seen in non-HIV-infected smallpox vaccine-naive participants who received the two-vial presentation in this study with the exception of fatigue (40.7% HIV-infected, 36.7% non-HIV infected).

Study 7 also evaluated the safety of a single dose of JYNNEOS two-vial presentation in 61 HIV-infected participants who previously received a smallpox vaccine and 30 non-HIV-infected participants who previously received a smallpox vaccine. Overall for participants who previously received a smallpox vaccine, the mean age was approximately 44 years, range 35-55 years; 44% women; 63.7% white/Caucasian; 34.1% black/African American; 2.2% other race. Participants were monitored for local and systemic adverse reactions for an 8-day period starting on the day of each vaccination. Solicited local adverse reactions reported among both HIV-infected and non HIV-infected participants previously vaccinated with a smallpox vaccine following a single dose of JYNNEOS two-vial presentation were redness (54.9%), pain (84.6%), induration (38.5%), swelling (45.1%), and itching (18.7%) at the injection site; solicited systemic adverse reactions reported following any dose of JYNNEOS were fatigue (38.5%), headache (37.4%), muscle pain (42.9%), nausea (27.5%), chills (16.5%), and fever (2.2%).

In HIV-infected participants with previous smallpox vaccine exposure who received the two-vial presentation, solicited local and systemic adverse reactions were reported at similar or lower frequencies compared to those reported in non-HIV-infected participants who previously received smallpox vaccination in this study.

Solicited Adverse Reactions in Individuals with Atopic Dermatitis:

The safety of JYNNEOS one-vial presentation in smallpox vaccine-naïve participants with currently active or a history of atopic dermatitis (AD) was evaluated in a multicenter, open-label clinical study (Study 8 [8]) conducted in the US and Mexico that included 350 participants with AD and 282 participants without AD. In the overall study the mean age of participants was 27 years (range 18-42 years), and participants were 59.0% women, 39.4% white/Caucasian, 10.9% Asian, 9.0% black/African American, 2.2% Other, and 38.4% Hispanic/Latino ethnicity. Demographic distribution was similar between participants with and without AD. In participants with AD, solicited local and systemic adverse reactions were reported at similar frequencies as those in participants without AD in this study, with the exception of redness (61.2% with AD vs. 49.3% without AD), swelling (52.2% with AD vs. 40.8% without AD), chills (15.9% with AD vs. 7.8% without AD) and headache (47.2% with AD vs. 34.8% without AD).

The safety of JYNNEOS two-vial presentation in smallpox vaccine-naïve participants with currently active or a history of atopic dermatitis (AD) was evaluated in an open-label, controlled clinical study (Study 9 [9]) conducted in Germany that included 31 participants with AD and 29 participants without AD. In the overall study, the mean age was approximately 25 years (range 19-34 years), and participants were 48.3% women, 95% white/Caucasian, 3.3% Asian, 1.7% black/African American; Hispanic/Latino ethnicity was not reported. The demographic distribution was similar between participants with AD and participants without AD. In participants with AD, solicited local and systemic adverse reactions were reported at similar frequencies as those in participants without AD in this study.

The following solicited local and systemic adverse reactions were reported at a greater frequency in participants with AD than those without AD in this study: redness (96.8% with AD vs. 89.7% without AD), itching (25.8% with AD vs. 13.8% without AD), fatigue (67.7% with AD vs. 51.7% without AD), headache (54.8% with AD vs. 44.8% without AD), myalgia (29% with AD vs. 24.1% without AD), and nausea (16.1% with AD vs. 10.3% without AD).

Serious Adverse Events

The integrated analyses of serious adverse events (SAEs) pooled safety data across 23 studies, which included a total of 8,222 smallpox vaccine-naïve participants and 766 smallpox vaccine-experienced participants who received at least 1 dose of JYNNEOS and 1,219 smallpox vaccine-naïve participants and 1 smallpox vaccine-experienced participant who received placebo only. SAEs were monitored from the day of the first study vaccination through at least 6 months after the last study vaccination.

Overall, SAEs were reported to occur in 1.5% (136/8,988) of JYNNEOS (one-vial or two-vial presentation) recipients and 1.4% (17/1,220) of placebo recipients. Among the smallpox vaccine-naïve participants, SAEs were reported for 1.3% (78/5,805) of JYNNEOS one-vial presentation recipients, 1.7% (40/2,417) of JYNNEOS two-vial presentation participants, and 1.4% (17/1,219) of placebo recipients. Among the smallpox vaccine-experienced participants enrolled in studies, SAEs were reported for 2.3% (15/654) of JYNNEOS one-vial presentation recipients and 2.7% (3/112) of JYNNEOS two-vial presentation recipients. Across all studies, a causal relationship to JYNNEOS could not be excluded for 5 SAEs, all non-fatal, which included Crohn’s disease, sarcoidosis, extraocular muscle paresis, throat tightness, and hemolytic anemia.

Cardiac Adverse Events of Special Interest

Evaluation of cardiac adverse events of special interest (AESIs) included any cardiac signs or symptoms, ECG changes determined to be clinically significant, or troponin-I elevated above 2 times the upper limit of normal. In the 23 studies, participants were monitored for cardiac-related signs or symptoms through at least 6 months after the last vaccination.

The numbers of JYNNEOS and placebo recipients, respectively, with troponin-I data were: baseline level (7,505 and 1,203); level two weeks after first dose (6,284 and 1,166); level two weeks after second dose (1,684 and 193); unscheduled visit, including for clinical evaluation of suspected cardiac adverse events (501 and 60).

Overall, cardiac AESIs were reported to occur in 1.3% (112/8,988) of JYNNEOS (one-vial or two-vial presentation) recipients and 0.2% (3/1,220) of placebo recipients. The higher proportion of JYNNEOS one-vial presentation recipients who experienced cardiac AESIs was driven by 28 cases of asymptomatic post-vaccination elevation of troponin-I in two studies: Study 6, which enrolled 482 HIV-infected participants and 97 healthy participants, and Study 8, which enrolled 350 participants with atopic dermatitis and 282 healthy participants. An additional 127 cases of asymptomatic post-vaccination elevation of troponin-I above the upper limit of normal but not above 2 times the upper limit of normal were documented in JYNNEOS recipients throughout the clinical development program, 124 of which occurred in Study 6 and Study 8. Proportions of participants with troponin-I elevations were similar between healthy and HIV-infected participants in Study 6 and between healthy and atopic dermatitis participants in Study 8. A different troponin assay was used in these two studies compared to the other studies, and these two studies had no placebo controls. The clinical significance of these asymptomatic post-vaccination elevations of troponin-I is unknown.

Among the cardiac AESIs reported, 6 cases (<0.1%) were considered to be causally related to JYNNEOS vaccination and included tachycardia, electrocardiogram T wave inversion, electrocardiogram abnormal, electrocardiogram ST segment elevation, electrocardiogram T wave abnormal, and palpitations.

None of the cardiac AESIs considered causally related to study vaccination were considered serious.

The following adverse reactions have been identified during postmarketing use of JYNNEOS. Because these reactions are reported voluntarily from a population of uncertain size, it is not always possible to reliably estimate their frequency or establish a causal relationship to vaccine exposure.

Cardiac Disorders: myocarditis, pericarditis

Immune System Disorders: hypersensitivity reactions, including angioedema, rash, and urticaria

Nervous System Disorders: dizziness, syncope, facial paralysis (Bell’s palsy), acute disseminated encephalomyelitis, myelin oligodendrocyte glycoprotein antibody-associated disease, bilateral optic neuritis

General disorders and administration site conditions: injection site warmth, injection site vesicles

All pregnancies have a risk of birth defect, loss, or other adverse outcomes. In the US general population, the estimated background risk of major birth defects and miscarriage in clinically recognized pregnancies is 2% to 4% and 15% to 20%, respectively. Available human data on JYNNEOS administered to pregnant women are insufficient to inform vaccine-associated risks in pregnancy.

The effect of JYNNEOS on embryo-fetal and post-natal development was evaluated in four developmental toxicity studies conducted in female rats and rabbits. In two studies, rats were administered a single human dose of JYNNEOS (0.5 mL) once prior to mating and on one or two occasions during gestation. In the third study, rats were administered a single human dose of JYNNEOS (0.5 mL) on two occasions during gestation. In the fourth study, rabbits were administered a single human dose of JYNNEOS (0.5 mL) once prior to mating and on two occasions during gestation. These animal studies revealed no evidence of harm to the fetus [see Data].

Animal Data

Developmental toxicity studies were conducted in female rats and rabbits. In one study, female rabbits were administered a single human dose of JYNNEOS (0.5 mL) by the subcutaneous route on three occasions: prior to mating, and on gestation days 0 and 14. Three studies were conducted in female rats administered a single human dose of JYNNEOS (0.5 mL) by the subcutaneous route on two or three occasions: prior to mating, and on gestation days 0 and 14; or prior to mating, and on gestation day 0; or on gestation days 0 and 6. No vaccine-related fetal malformations or variations and adverse effects on female fertility or pre-weaning development were reported in these studies.

It is not known whether JYNNEOS is excreted in human milk. Data are not available to assess the effects of JYNNEOS in the breastfed infant or on milk production/excretion.

The development and health benefits of breastfeeding should be considered along with the mother’s clinical need for JYNNEOS and any potential adverse effects on the breastfed child from JYNNEOS or from the underlying maternal condition. For preventive vaccines, the underlying condition is susceptibility to disease prevented by the vaccine.

Safety and effectiveness of JYNNEOS have not been established in individuals less than 18 years of age.

Forty-two smallpox vaccine-experienced adults 65 to 80 years of age received at least one dose of JYNNEOS (Study 5).

Clinical studies of JYNNEOS did not include sufficient numbers of individuals aged 65 and over to determine whether they respond differently from younger individuals.

JYNNEOS (Smallpox and Mpox Vaccine, Live, Non-replicating) is a sterile injectable suspension administered subcutaneously.

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JYNNEOS is a live vaccine produced from the strain Modified Vaccinia Ankara-Bavarian Nordic (MVA-BN), an attenuated, non-replicating orthopoxvirus. MVA-BN is grown in primary Chicken Embryo Fibroblast (CEF) cells suspended in a serum-free medium containing no material of direct animal origin, harvested from the CEF cells, purified and concentrated by several Tangential Flow Filtration (TFF) steps including benzonase digestion.

{ "type": "p", "children": [], "text": "JYNNEOS is a live vaccine produced from the strain Modified Vaccinia Ankara-Bavarian Nordic (MVA-BN), an attenuated, non-replicating orthopoxvirus. MVA-BN is grown in primary Chicken Embryo Fibroblast (CEF) cells suspended in a serum-free medium containing no material of direct animal origin, harvested from the CEF cells, purified and concentrated by several Tangential Flow Filtration (TFF) steps including benzonase digestion." }

Each 0.5 mL dose of JYNNEOS is formulated to contain 0.5 x 108 to 3.95 x 108 infectious units of MVA-BN live virus. Each 0.5 mL dose contains 0.61 mg of Tris (tromethamine), 4.09 mg sodium chloride, and may contain residual amounts of host-cell DNA (≤20 mcg), protein (≤500 mcg), benzonase (≤0.0025 mcg), gentamicin (≤0.400 mcg), and ciprofloxacin (≤0.005 mcg). In addition, JYNNEOS vaccine reconstituted with Diluent Component (Water for Injection) contains 9.45 mg dextran 40, 22.5 mg sucrose, and 0.054 mg potassium L-glutamate monohydrate as stabilizers. After preparation [see Dosage and Administration (2.2)], JYNNEOS is a milky, light yellow to pale white colored suspension.

{ "type": "p", "children": [], "text": "Each 0.5 mL dose of JYNNEOS is formulated to contain 0.5 x 108 to 3.95 x 108 infectious units of MVA-BN live virus. Each 0.5 mL dose contains 0.61 mg of Tris (tromethamine), 4.09 mg sodium chloride, and may contain residual amounts of host-cell DNA (≤20 mcg), protein (≤500 mcg), benzonase (≤0.0025 mcg), gentamicin (≤0.400 mcg), and ciprofloxacin (≤0.005 mcg). In addition, JYNNEOS vaccine reconstituted with Diluent Component (Water for Injection) contains 9.45 mg dextran 40, 22.5 mg sucrose, and 0.054 mg potassium L-glutamate monohydrate as stabilizers. After preparation [see Dosage and Administration (2.2)], JYNNEOS is a milky, light yellow to pale white colored suspension." }

JYNNEOS is formulated without preservatives. The vial stoppers are not made with natural rubber latex.

{ "type": "p", "children": [], "text": "JYNNEOS is formulated without preservatives. The vial stoppers are not made with natural rubber latex." }

JYNNEOS is an attenuated, live, non-replicating smallpox and mpox vaccine that elicits humoral and cellular immune responses to orthopoxviruses. Vaccinia neutralizing antibody responses in humans were evaluated to establish the effectiveness of JYNNEOS for prevention of smallpox and mpox.

JYNNEOS has not been evaluated for carcinogenic or mutagenic potential, or for impairment of male fertility in animals. Developmental toxicity studies conducted in rats and rabbits vaccinated with JYNNEOS revealed no evidence of impaired female fertility [see Use in Specific Populations (8.1)].

The efficacy of JYNNEOS to protect cynomolgus macaques (Macaca fascicularis) against a monkeypox virus (MPXV) challenge was evaluated in several studies. Animals were administered Tris-Buffered Saline (placebo) or JYNNEOS (1 x 108 TCID50) subcutaneously on day 0 and day 28. On day 63, animals were challenged with MPXV delivered by aerosol (3 x 105 pfu), intravenous (5 x 107 pfu) or intratracheal (5 x 106 pfu) route. Across all studies, 80-100% of JYNNEOS-vaccinated animals survived compared to 0-40% of control animals.

Vaccine effectiveness against smallpox was inferred by comparing the immunogenicity of JYNNEOS to a licensed smallpox vaccine (ACAM2000) based on a Plaque Reduction Neutralization Test (PRNT) using the Western Reserve strain of vaccinia virus and was supported by efficacy data from animal challenge studies. [see Nonclinical Toxicology (13.2)]

Vaccine effectiveness against mpox was inferred from the immunogenicity of JYNNEOS in a clinical study and from efficacy data from animal challenge studies. [see Nonclinical Toxicology (13.2)]

Study 10 [10] (N=433) was a randomized, open-label study conducted at US military facilities in South Korea to compare the immunogenicity of JYNNEOS to ACAM2000 in healthy smallpox vaccine-naïve adults 18 through 42 years of age. Participants were randomized to receive either two doses of JYNNEOS (N=220) administered 28 days apart or one dose of ACAM2000 (N=213). In the total study population, the mean age was 24 years and 23 years in participants receiving JYNNEOS and ACAM2000, respectively; 82.3% and 86.4% of the participants were men; 57.3% and 63.8% were white/Caucasian, 21.8% and 18.8% black/African American, 6.4% and 5.6% Asian, 3.6% and 2.8% American Indian/Alaska Native, 2.3% and 1.4% Native Hawaiian/Other Pacific, 8.6% and 7.5% other racial groups, and 24.5% and 18.8% of Hispanic/Latino ethnicity (JYNNEOS and ACAM2000, respectively).

The primary immunogenicity endpoint was geometric mean titer (GMT) of vaccinia neutralizing antibodies assessed by PRNT at “peak visits” defined as two weeks after the second dose of JYNNEOS and four weeks after the single dose of ACAM2000. Analyses of antibody responses were performed in the per-protocol immunogenicity (PPI) population, consisting of participants who received all vaccinations and completed all visits up until two weeks after the second dose of JYNNEOS without major protocol violations pertaining to immunogenicity assessments. Table 3 presents the pre-vaccination and “peak visit” PRNT GMTs from Study 10.

<div class="scrollingtable"><table cellpadding="3.6pt" width="100%"> <caption> <span>Table 3: Comparison of Vaccinia-Neutralizing Antibody Responses Following Vaccination with JYNNEOS or ACAM2000 in Healthy Smallpox Vaccine-Naïve Adults 18 through 42 Years of Age, Study 10<span class="Sup">x</span>, Per Protocol Set for Immunogenicity<span class="Sup">y</span></span> </caption> <col width="21%"/> <col width="40%"/> <col width="40%"/> <thead> <tr class="First Last"> <th align="left" class="Botrule Lrule Rrule Toprule" valign="top"><span class="Bold">Time Point </span></th><th align="center" class="Botrule Lrule Rrule Toprule" valign="top"><span class="Bold">JYNNEOS<span class="Sup">a</span> (N=185)</span> <br/> <span class="Bold">GMT<span class="Sup">b</span> [95% CI]</span></th><th align="center" class="Botrule Lrule Rrule Toprule" valign="top"><span class="Bold">ACAM2000<span class="Sup">a</span> (N=186)</span> <br/> <span class="Bold">GMT<span class="Sup">b</span> [95% CI]</span></th> </tr> </thead> <tfoot> <tr class="First Last"> <td align="left" colspan="3" valign="top"><span class="Sup">x</span>   NCT01913353<br/> <span class="Sup">y</span>   Per Protocol Set for Immunogenicity included participants who received all vaccinations, completed all visits up until the specified “peak visits” (two weeks after the second dose of JYNNEOS or 4 weeks after the single dose of ACAM2000) without major protocol violations pertaining to immunogenicity assessments.<br/> <span class="Sup">a</span>   JYNNEOS was administered as a series of two doses given 28 days apart, and ACAM2000 was administered as a single dose.<br/> <span class="Sup">b</span>   GMT of vaccinia-neutralizing antibody titers assessed by plaque reduction neutralization test (PRNT) using the Western Reserve vaccinia strain. Values below the assay lower limit of quantitation (LLOQ) of 20 were imputed to a titer of 10; the proportions of participants with pre-vaccination titers less than the assay lower limit of detection were 98.9% among participants randomized to JYNNEOS and 97.8% among participants randomized to ACAM2000, respectively.<br/> <span class="Sup">c</span>   Non-inferiority of the “peak visit” PRNT GMT for JYNNEOS compared to ACAM2000 was demonstrated as the lower bound of the 1-sided 97.5% CI for the GMT ratio (JYNNEOS/ACAM2000) was &gt; 0.5.<br/>N: Number of participants in the specified treatment group; GMT: Geometric Mean Titer; 95% CI: 95% confidence interval, lower limit and upper limit.</td> </tr> </tfoot> <tbody> <tr class="First"> <td class="Botrule Lrule Rrule" valign="top"> <p class="First">Pre-Vaccination</p> </td><td align="center" class="Botrule Lrule Rrule Toprule" valign="top"> <p class="First">10.1 [9.9, 10.2]</p> </td><td align="center" class="Botrule Lrule Rrule Toprule" valign="top"> <p class="First">10.0 [10.0, 10.0]</p> </td> </tr> <tr class="Last"> <td class="Botrule Lrule Rrule Toprule" valign="top"> <p class="First">Post-Vaccination<br/>“Peak Visit”<span class="Sup">y</span> </p> </td><td align="center" class="Botrule Lrule Rrule Toprule" valign="middle"> <p class="First">152.8<span class="Sup">c</span> [133.3, 175.0]</p> </td><td align="center" class="Botrule Lrule Rrule Toprule" valign="middle"> <p class="First">84.4<span class="Sup">c</span> [73.4, 97.0]</p> </td> </tr> </tbody> </table></div>

PRNT GMTs were also evaluated at pre-specified time points post-vaccination and prior to two weeks after the second dose of JYNNEOS. The PRNT GMTs at two and four weeks after the first dose of JYNNEOS (prior to the second dose), were 23.4 (95% CI: 20.5, 26.7) and 23.5 (95% CI: 20.6, 26.9), respectively. The PRNT GMT at two weeks after the single dose of ACAM2000 was 23.7 (95% CI: 20.9, 26.8).

Study 2 [2] was a randomized, double-blind, multicenter study conducted in the US to assess non-inferiority of immune responses induced by the two-vial presentation of JYNNEOS compared to immune responses induced by the one-vial presentation of JYNNEOS in healthy smallpox vaccine-naïve adults 18 through 55 years of age [see Adverse Reactions (6.1)]. In the Per Protocol Set (PPS; one-vial: N=297; two-vial: N=306), consisting of participants who received all vaccinations and completed all visits up until two weeks after the second dose of JYNNEOS without major protocol violations, the mean age was 28 years for both study groups; 52.9% of the participants in both study groups were women; 72.7% of the participants administered the one-vial presentation of JYNNEOS and 75.2% of the participants administered the two-vial presentation of JYNNEOS were White/Caucasian, 24.2% and 21.9% were Black/African American, respectively, 1.0% and 0% Oriental/Asian, 0% and 0.3% American Indian/Alaska Native, 0.3% and 0.3% Native Hawaiian/Other Pacific, 1.7% and 1.6% multiple racial groups, 0% and 0.7% other racial groups, and 27.3% and 27.5% of Hispanic/Latino ethnicity, respectively.

The primary immunogenicity endpoint was GMT of anti-vaccinia antibodies assessed by Enzyme-linked Immunosorbent Assay (ELISA), and a secondary immunogenicity endpoint was GMT of vaccinia-specific neutralizing antibodies assessed by PRNT, at two weeks after the second dose of JYNNEOS. Analyses of antibody responses were performed on the PPS. Table 4 presents the pre-and post-vaccination ELISA and PRNT GMTs from Study 2.

<div class="scrollingtable"><table class="Noautorules" width="100%"> <caption> <span>Table 4: Comparison of Antibody Responses Following Vaccination with One-Vial or Two-Vial Presentations of JYNNEOS in Healthy Smallpox Vaccine-Naïve Adults 18 through 55 Years of Age, Study 2<span class="Sup">x</span>, Per Protocol Set<span class="Sup">y</span></span> </caption> <col width="20%"/> <col width="20%"/> <col width="20%"/> <col width="20%"/> <col width="20%"/> <tfoot> <tr> <td align="left" colspan="5" valign="top"><span class="Sup">x</span>   NCT01668537<br/> <span class="Sup">y</span>   Per Protocol Set included participants who received all vaccinations, completed all visits without major protocol violations.<br/> <span class="Sup">a</span>   JYNNEOS was administered as a series of two doses given 4 weeks apart.<br/> <span class="Sup">b</span>   GMT of anti-vaccinia antibody titers assessed by Enzyme-linked Immunosorbent Assay (ELISA). Values below the assay lower limit of quantitation (LLOQ) of 100 were imputed to a titer of 50; the proportions of participants with prevaccination titers less than the assay lower limit of detection were 98.0% among participants randomized to one-vial JYNNEOS and 97.7% among participants randomized to two-vial JYNNEOS.<br/> <span class="Sup">c</span>   GMT of vaccinia-neutralizing antibody titers assessed by Plaque Reduction Neutralization Test (PRNT). Values below the assay LLOQ of 20 were imputed to a titer of 10; the proportions of participants with pre-vaccination titers less than the assay lower limit of detection were 98.0% among participants randomized to one-vial JYNNEOS and 98.7% among participants randomized to two-vial JYNNEOS.<br/> <span class="Sup">d</span>   Non-inferiority of the ELISA GMT for JYNNEOS was demonstrated as the upper bound of the 2-sided 95% CI for the GMT ratio (one-vial JYNNEOS/two-vial JYNNEOS) was below the margin of 1.5.<br/>N: Number of participants in the specified treatment group; GMT: Geometric Mean Titer; 95% CI: 95% confidence interval, lower limit and upper limit.</td> </tr> </tfoot> <tbody class="Headless"> <tr> <td align="center" class="Botrule Lrule Rrule Toprule" rowspan="2" valign="middle"> <p class="First"> <span class="Bold">Time Point</span> </p> </td><td align="center" class="Botrule Lrule Rrule Toprule" colspan="2" valign="middle"> <p class="First"> <span class="Bold">ELISA</span> </p> </td><td align="center" class="Botrule Lrule Rrule Toprule" colspan="2" valign="middle"> <p class="First"> <span class="Bold">PRNT</span> </p> </td> </tr> <tr> <td align="center" class="Botrule Lrule Rrule Toprule" valign="middle"> <p class="First"> <span class="Bold">JYNNEOS<span class="Sup">a</span></span> </p> <p> <span class="Bold">One-Vial</span> </p> <p> <span class="Bold">Presentation</span> </p> <p> <span class="Bold">(N=297)</span> </p> <p> <span class="Bold">GMT<span class="Sup">b</span> [95% CI]</span> </p> </td><td align="center" class="Botrule Lrule Rrule Toprule" valign="middle"> <p class="First"> <span class="Bold">JYNNEOS<span class="Sup">a</span></span> </p> <p> <span class="Bold">Two-Vial</span> </p> <p> <span class="Bold">Presentation</span> </p> <p> <span class="Bold">(N=306)</span> </p> <p> <span class="Bold">GMT<span class="Sup">b</span> [95% CI]</span> </p> </td><td align="center" class="Botrule Lrule Rrule Toprule" valign="middle"> <p class="First"> <span class="Bold">JYNNEOS<span class="Sup">a</span></span> </p> <p> <span class="Bold">One-Vial</span> </p> <p> <span class="Bold">Presentation</span> </p> <p> <span class="Bold">(N=297)</span> </p> <p> <span class="Bold">GMT<span class="Sup">c</span> [95% CI]</span> </p> </td><td align="center" class="Botrule Lrule Rrule Toprule" valign="middle"> <p class="First"> <span class="Bold">JYNNEOS<span class="Sup">a</span></span> </p> <p> <span class="Bold">Two-Vial</span> </p> <p> <span class="Bold">Presentation</span> </p> <p> <span class="Bold">(N=306)</span> </p> <p> <span class="Bold">GMT<span class="Sup">c</span> [95% CI]</span> </p> </td> </tr> <tr> <td class="Botrule Lrule Rrule" valign="top"> <p class="First">Pre-Vaccination</p> </td><td align="center" class="Botrule Lrule Rrule Toprule" valign="top"> <p class="First">50.5 [49.7, 51.2]</p> </td><td align="center" class="Botrule Lrule Rrule Toprule" valign="top"> <p class="First">50.3 [49.7, 51.0]</p> </td><td align="center" class="Botrule Lrule Rrule Toprule" valign="top"> <p class="First">10.2 [9.9, 10.4]</p> </td><td align="center" class="Botrule Lrule Rrule Toprule" valign="top"> <p class="First">10.1 [10.0, 10.3]</p> </td> </tr> <tr> <td class="Botrule Lrule Rrule Toprule" valign="top"> <p class="First">Two Weeks Post</p> <p>Dose 2<span class="Sup">y</span> </p> </td><td align="center" class="Botrule Lrule Rrule Toprule" valign="top"> <p class="First">875.1<span class="Sup">d</span> [801.3,</p> <p>955.7]</p> </td><td align="center" class="Botrule Lrule Rrule Toprule" valign="top"> <p class="First">1099.6<span class="Sup">d</span> [1014.8,</p> <p>1191.6]</p> </td><td align="center" class="Botrule Lrule Rrule Toprule" valign="top"> <p class="First">82.7 [74.3, 92.1]</p> </td><td align="center" class="Botrule Lrule Rrule Toprule" valign="top"> <p class="First">100.5 [90.3, 111.8]</p> </td> </tr> </tbody> </table></div>

1.      Study 1: NCT011446372.      Study 2: NCT016685373.      Study 3: NCT003165244.      Study 4: NCT006865825.      Study 5: NCT008574936.      Study 6: NCT003165897.      Study 7: NCT001899048.      Study 8: NCT003166029.      Study 9: NCT0018991710.    Study 10: NCT01913353

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How Supplied

JYNNEOS one-vial presentation is supplied in cartons containing either:

<div class="scrollingtable"><table class="Noautorules" width="100%"> <caption> <span>Table 4: JYNNEOS One-Vial Presentation</span> </caption> <col width="33%"/> <col width="33%"/> <col width="33%"/> <tbody class="Headless"> <tr> <td align="center" class="Botrule Lrule Rrule Toprule" valign="middle"> <p class="First"> <span class="Bold">Carton</span> </p> </td><td align="center" class="Botrule Lrule Rrule Toprule" valign="middle"> <p class="First"> <span class="Bold">Carton NDC Number</span> </p> </td><td align="center" class="Botrule Lrule Rrule Toprule" valign="middle"> <p class="First"> <span class="Bold">Vial NDC Number</span> </p> </td> </tr> <tr> <td align="center" class="Botrule Lrule Rrule" valign="middle"> <p class="First">Carton of 10 vials</p> </td><td align="center" class="Botrule Lrule Rrule Toprule" valign="middle"> <p class="First">50632-023-02</p> </td><td align="center" class="Botrule Lrule Rrule Toprule" valign="middle"> <p class="First">50632-023-04</p> </td> </tr> <tr> <td align="center" class="Botrule Lrule Rrule Toprule" valign="middle"> <p class="First">Carton of 20 vials</p> </td><td align="center" class="Botrule Lrule Rrule Toprule" valign="middle"> <p class="First">50632-022-02</p> </td><td align="center" class="Botrule Lrule Rrule Toprule" valign="middle"> <p class="First">50632-022-04</p> </td> </tr> </tbody> </table></div>

Storage Conditions

Keep frozen at -25°C to -15°C (-13°F to +5°F).

Store in the original package to protect from light.

Do not re-freeze a vial once it has been thawed.

Once thawed, the vaccine may be kept at +2°C to +8°C (+36°F to +46°F) for 4 weeks.

Do not use the vaccine after the expiration.

How Supplied

JYNNEOS two-vial presentation is supplied in separate cartons:

To form a single dose of JYNNEOS, reconstitute one vial of Lyophilized Antigen Component (Vial A, yellow cap) with one vial of Diluent Component (Vial B, blue cap).

<div class="scrollingtable"><table class="Noautorules" width="100%"> <caption> <span>Table 5: JYNNEOS Two-Vial Presentation</span> </caption> <col width="33%"/> <col width="33%"/> <col width="33%"/> <tbody class="Headless"> <tr> <td align="center" class="Botrule Lrule Rrule Toprule" valign="middle"> <p class="First"> <span class="Bold">Carton</span> </p> </td><td class="Botrule Lrule Rrule Toprule" valign="middle"> <p class="First"> <span class="Bold">Carton NDC Number</span> </p> </td><td class="Botrule Lrule Rrule Toprule" valign="middle"> <p class="First"> <span class="Bold">Vial NDC Number</span> </p> </td> </tr> <tr> <td class="Botrule Lrule Rrule" valign="middle"> <p class="First">Carton of 20 vials of Lyophilized</p> <p>Antigen Component</p> </td><td class="Botrule Lrule Rrule Toprule" valign="middle"> <p class="First">50632-002-02</p> </td><td class="Botrule Lrule Rrule Toprule" valign="middle"> <p class="First">50632-002-01</p> </td> </tr> <tr> <td class="Botrule Lrule Rrule Toprule" valign="middle"> <p class="First">Carton of 20 vials of Diluent</p> <p>Component</p> </td><td class="Botrule Lrule Rrule Toprule" valign="middle"> <p class="First">50632-003-02</p> </td><td class="Botrule Lrule Rrule Toprule" valign="middle"> <p class="First">50632-003-01</p> </td> </tr> </tbody> </table></div>

Storage Before Reconstitution

Storage After Reconstitution

After reconstitution, use immediately or store refrigerated at +2°C to +8°C (+36°F to +46°F), away from light, for up to 12 hours. Do not freeze reconstituted vaccine.

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Manufactured by: Bavarian Nordic A/SPhilip Heymans Alle 32900 HellerupDenmark

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NDC 50632-023-02

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Smallpox and Mpox                            Rx only Vaccine, Live, Non-replicating

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JYNNEOS®

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Suspension for subcutaneous injection

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Contents: 10 single dose vials

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BAVARIAN NORDIC

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NDC 50632-022-02

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Smallpox and Mpox                            Rx only Vaccine, Live, Non-replicating

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JYNNEOS®

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Suspension for subcutaneous injection

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Contains 20 single-dose 0.5 mL vials

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BAVARIAN NORDIC

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Vial Label – NDC 50632-023-04

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Vial Label - NDC 50632-022-04

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Smallpox and Mpox Vaccine, Live,Non-replicating

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JYNNEOS®

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Single-dose: 0.5 mL

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Bavarian Nordic A/S

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U.S. Govt. Lic. No. 2096

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VILA-XXXX-XX

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LOT: XXXXXXXX

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EXP: MM-YYYY

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NDC 50632-002-02                            Rx only

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IMPORTANT: Lyophilized Antigen Component andSterile Water Diluent Component must be combinedbefore use.

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Smallpox and Mpox Vaccine,Live, Non-replicating

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JYNNEOS®

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STORE FROZEN

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Injectable suspension, for subcutaneous use.

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Contents: 20 vials of Lyophilized Antigen ComponentReconstitute Lyophilized Antigen Component (Vial A)with Diluent Component (Vial B) to form a single doseof JYNNEOS.

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After reconstitution, a single dose of JYNNEOS is 0.5 mL.

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BAVARIAN NORDIC

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NDC 50632-002-01          Rx only

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Lyophilized AntigenComponent

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NOT TO BE USED ALONE

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Reconstitute with Diluent Componentto form Smallpox and Mox VaccineLive, Non-replicating (JYNNEOS).After reconstitution, a single dose ofJYNNEOS is 0.5 mL

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LOT:

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EXP:

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Mfd. by Bavarian Nordic A/S

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VILA-XXXX-XX

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NDC 50632-003-02                            Rx only

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Diluent Component

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NOT TO BE USED ALONE

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Use Diluent Component (Vial B) to reconstitute LyophilizedAntigen Component (Vial A) to form a single dose of Smallpoxand Mpox Vaccine, Live, Non-replicating (JYNNEOS).

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Contents: 20 vials of Diluent Component.

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Contains no preservative.

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See prescribing information is accompanying LyophilizedAntigen Component Package A for additional information.

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BAVARIAN NORDIC

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NDC 50632-003-01                Rx only

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Diluent Component

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NOT TO BE USED ALONE

{ "type": "p", "children": [], "text": "\nNOT TO BE USED ALONE\n" }

Use to reconstitute LyophilizedAntigen Component (Vial A) to form Smallpox and Mpox Vaccine, Live, Non-replicating (JYNNEOS).

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Mfg. by Bavarian Nordic A/S.

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LOT:

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EXP:

{ "type": "p", "children": [], "text": "EXP:" }

Mfd. by Bavarian Nordic A/S

{ "type": "p", "children": [], "text": "Mfd. by Bavarian Nordic A/S" }

VILA-XXXX-XX

{ "type": "p", "children": [], "text": "VILA-XXXX-XX" }

ABRYSVO is a vaccine indicated for active immunization of pregnant individuals at 32 through 36 weeks gestational age for the prevention of lower respiratory tract disease (LRTD) and severe LRTD caused by respiratory syncytial virus (RSV) in infants from birth through 6 months of age.

ABRYSVO is a vaccine indicated for active immunization for the prevention of LRTD caused by RSV in individuals 60 years of age and older.

ABRYSVO is a vaccine indicated for active immunization for the prevention of LRTD caused by RSV in individuals 18 through 59 years of age who are at increased risk for LRTD caused by RSV.

After reconstitution, a single dose of ABRYSVO is either 0.5 mL (Act-O-Vial presentation and vial and vial presentation) or approximately 0.5 mL (vial and prefilled syringe presentation) [see Dosage and Administration (2.2)].

ABRYSVO is supplied in 3 presentations as follows:

Act-O-Vial Presentation

The Act-O-Vial presentation is supplied in cartons. Each Act-O-Vial contains the Lyophilized Antigen Component (a sterile white powder) and Sterile Water Diluent Component.

Vial and Prefilled Syringe Presentation

The vial and prefilled syringe presentation is supplied in cartons containing a kit(s). Each kit includes a vial of Lyophilized Antigen Component (a sterile white powder), a prefilled syringe containing Sterile Water Diluent Component, and a vial adapter.

Vial and Vial Presentation

The vial and vial presentation is supplied in cartons that include vials of Lyophilized Antigen Component (a sterile white powder) and vials containing Sterile Water Diluent Component.

For all presentations, reconstitute the Lyophilized Antigen Component with the Sterile Water Diluent Component to form ABRYSVO, as described in the instructions below.

Reconstitution Instructions for the Act-O-Vial Presentation

<div class="scrollingtable"><table class="Noautorules" width="100%"> <col width="31%"/> <col width="35%"/> <col width="33%"/> <tbody class="Headless"> <tr> <td valign="top"><a name="id392937932"></a><img alt="AoV" src="/dailymed/image.cfm?name=abrysvo-01.jpg&amp;setid=be18292e-b1a2-4815-a0ed-003efaa6bea3"/></td><td valign="top"><a name="id733749738"></a><img alt="AoV_Step1" src="/dailymed/image.cfm?name=abrysvo-02.jpg&amp;setid=be18292e-b1a2-4815-a0ed-003efaa6bea3"/></td><td valign="top"><a name="id249087401"></a><img alt="AoV_Step2" src="/dailymed/image.cfm?name=abrysvo-03.jpg&amp;setid=be18292e-b1a2-4815-a0ed-003efaa6bea3"/></td> </tr> <tr> <td valign="top"> <p class="First" style="border-left:1px solid;"> <span class="XmChange">Act-O-Vial presentation</span> </p> </td><td valign="top"> <p class="First" style="border-left:1px solid;"> <span class="XmChange">Step 1. Reconstitution of the Lyophilized Antigen Component with the Sterile Water Diluent Component to form ABRYSVO </span> <br/> <br/> <span class="XmChange">Place the Act-O-Vial on a flat surface and firmly press down on the plastic activator cap to release the center stopper and Sterile Water Diluent Component into the lower chamber.</span> <br/> <br/> <span class="XmChange">Gently swirl the Act-O-Vial until the powder is completely dissolved. </span> <br/> <br/> <span class="XmChange">Do not shake.</span> </p> </td><td valign="top"> <p class="First" style="border-left:1px solid;"> <span class="XmChange">Step 2. Withdrawal of ABRYSVO</span> <br/> <br/> <span class="XmChange">Remove the plastic tab covering the center of the top stopper.</span> <br/> <br/> <span class="XmChange">Using a sterile needle and syringe, insert the needle straight through the <span class="Bold">center </span>of the stopper.</span> <br/> <br/> <span class="XmChange">Invert the Act-O-Vial and withdraw 0.5 mL of ABRYSVO.</span> <br/> <br/> <span class="XmChange">Discard the Act-O-Vial and excess volume after withdrawal of a single dose.</span> </p> </td> </tr> </tbody> </table></div>

Reconstitution Instructions for Vial and Prefilled Syringe Presentation

<div class="scrollingtable"><table class="Noautorules" width="100%"> <col width="29%"/> <col width="24%"/> <col width="29%"/> <col width="18%"/> <tbody class="Headless"> <tr> <td valign="top"><a name="id-1167700780"></a><img alt="Step1-VP" src="/dailymed/image.cfm?name=abrysvo-04.jpg&amp;setid=be18292e-b1a2-4815-a0ed-003efaa6bea3"/></td><td valign="top"><a name="id-541288223"></a><img alt="Step 2-VP" src="/dailymed/image.cfm?name=abrysvo-05.jpg&amp;setid=be18292e-b1a2-4815-a0ed-003efaa6bea3"/></td><td valign="top"><a name="id1794791018"></a><img alt="Step 3-VP" src="/dailymed/image.cfm?name=abrysvo-06.jpg&amp;setid=be18292e-b1a2-4815-a0ed-003efaa6bea3"/></td><td valign="top"><a name="id-1147360449"></a><img alt="Step 4-VP" src="/dailymed/image.cfm?name=abrysvo-07.jpg&amp;setid=be18292e-b1a2-4815-a0ed-003efaa6bea3"/></td> </tr> <tr> <td valign="top"> <p class="First" style="border-left:1px solid;"> <span class="XmChange">Step 1. Attachment of the vial adapter to the vial</span> <br/> <br/> <span class="XmChange">Remove the flip top cap from the vial of Lyophilized Antigen Component.</span> <br/> <br/> <span class="XmChange">Peel off the top cover from the vial adapter packaging.</span> <br/> <br/> <span class="XmChange">While keeping the vial adapter in its packaging, center the adapter over the vial’s stopper and attach to the vial with a straight downward push.</span> <br/> <br/> <span class="XmChange">Remove the packaging.</span> </p> </td><td valign="top"> <p class="First" style="border-left:1px solid;"> <span class="XmChange">Step 2. Connection of the syringe to the vial adapter</span> <br/> <br/> <span class="XmChange">Hold the syringe of Sterile Water Diluent Component by the Luer lock adapter.</span> <br/> <br/> <span class="XmChange">Twist to remove the syringe cap.</span> <br/> <br/> <span class="XmChange">Connect the syringe to the vial adapter by turning the Luer lock.</span> </p> </td><td valign="top"> <p class="First" style="border-left:1px solid;"> <span class="XmChange">Step 3. Reconstitution of the Lyophilized Antigen Component with the Sterile Water Diluent Component to form ABRYSVO</span> <br/> <br/> <span class="XmChange">Inject the entire contents of the syringe into the vial.</span> <br/> <br/> <span class="XmChange">Hold the plunger rod down and gently swirl the vial until the powder is completely dissolved.</span> <br/> <br/> <span class="XmChange">Do not shake.</span> </p> </td><td valign="top"> <p class="First" style="border-left:1px solid;"> <span class="XmChange">Step 4. Withdrawal of ABRYSVO</span> <br/> <br/> <span class="XmChange">Invert the vial completely and slowly withdraw the entire contents into the syringe for an approximately 0.5 mL dose of ABRYSVO.</span> <br/> <br/> <span class="XmChange">Twist to disconnect the syringe from the vial adapter.</span> <br/> <br/> <span class="XmChange">Attach a sterile needle suitable for intramuscular injection.</span> </p> </td> </tr> </tbody> </table></div>

Reconstitution Instructions for the Vial and Vial Presentation

<div class="scrollingtable"><table class="Noautorules" width="100%"> <col width="25%"/> <col width="25%"/> <col width="25%"/> <col width="25%"/> <tbody class="Headless"> <tr> <td valign="top"><a name="id-676274793"></a><img alt="Step 1-VV" src="/dailymed/image.cfm?name=abrysvo-08.jpg&amp;setid=be18292e-b1a2-4815-a0ed-003efaa6bea3"/></td><td valign="top"><a name="id536094787"></a><img alt="Step 2a-VV" src="/dailymed/image.cfm?name=abrysvo-09.jpg&amp;setid=be18292e-b1a2-4815-a0ed-003efaa6bea3"/></td><td valign="top"><a name="id230515992"></a><img alt="Step 2b-VV" src="/dailymed/image.cfm?name=abrysvo-10.jpg&amp;setid=be18292e-b1a2-4815-a0ed-003efaa6bea3"/></td><td valign="top"><a name="id-1023247155"></a><img alt="Step 3-VV" src="/dailymed/image.cfm?name=abrysvo-11.jpg&amp;setid=be18292e-b1a2-4815-a0ed-003efaa6bea3"/></td> </tr> <tr> <td valign="top"> <p class="First" style="border-left:1px solid;"> <span class="XmChange">Step 1. Withdrawal of the Sterile Water Diluent</span> <br/> <br/> <span class="XmChange">Using a sterile needle and sterile syringe, withdraw the entire contents of the vial containing the Sterile Water Diluent Component.</span> </p> </td><td colspan="2" valign="top"> <p class="First" style="border-left:1px solid;"> <span class="XmChange">Step 2. Reconstitution of the Lyophilized Antigen Component with the Sterile Water Diluent Component to form ABRYSVO</span> <br/> <br/> <span class="XmChange">Inject the entire contents into the vial containing the Lyophilized Antigen Component (white powder). Gently swirl the vial in a circular motion until the powder is completely dissolved. Do not shake.</span> </p> </td><td valign="top"> <p class="First" style="border-left:1px solid;"> <span class="XmChange">Step 3. Withdrawal of ABRYSVO</span> <br/> <br/> <span class="XmChange">Withdraw 0.5 mL from the vial containing the reconstituted vaccine.</span> <br/> <br/> <span class="XmChange">Discard the vial and any excess volume after withdrawal of a single dose.</span> </p> </td> </tr> </tbody> </table></div>

For intramuscular injection

After reconstitution, ABRYSVO is a clear and colorless solution. Parenteral drug products should be inspected visually for particulate matter and discoloration prior to administration, whenever solution and container permit. Discard if either condition is present.

Administer ABRYSVO immediately or store at room temperature [15°C to 30°C (59°F to 86°F)] and use within 4 hours. Discard reconstituted vaccine if not used within 4 hours.

For injection.

{ "type": "p", "children": [], "text": "For injection." }

For the Act-O-Vial presentation, a single dose after reconstitution is 0.5 mL.

{ "type": "p", "children": [], "text": "For the Act-O-Vial presentation, a single dose after reconstitution is 0.5 mL." }

For the vial and prefilled syringe presentation, a single dose after reconstitution is approximately 0.5 mL.

{ "type": "p", "children": [], "text": "For the vial and prefilled syringe presentation, a single dose after reconstitution is approximately 0.5 mL." }

For the vial and vial presentation, a single dose after reconstitution is 0.5 mL.

{ "type": "p", "children": [], "text": "For the vial and vial presentation, a single dose after reconstitution is 0.5 mL." }

Do not administer ABRYSVO to individuals with a history of a severe allergic reaction (e.g., anaphylaxis) to any component of ABRYSVO [see Description (11)].

{ "type": "p", "children": [], "text": "Do not administer ABRYSVO to individuals with a history of a severe allergic reaction (e.g., anaphylaxis) to any component of ABRYSVO [see Description (11)]." }

The results of a postmarketing observational study suggest an increased risk of Guillain‑Barré syndrome (GBS) during the 42 days following vaccination with ABRYSVO [see Adverse Reactions (6.2)].

A numerical imbalance in preterm births in ABRYSVO recipients was observed compared to placebo recipients in two clinical studies [see Adverse Reactions (6.1)]. Available data are insufficient to establish or exclude a causal relationship between preterm birth and ABRYSVO. To avoid the potential risk of preterm birth with use of ABRYSVO before 32 weeks of gestation, administer ABRYSVO as indicated in pregnant individuals at 32 through 36 weeks gestational age. Pregnant individuals who were at increased risk of preterm birth were generally excluded from clinical studies of ABRYSVO.

Appropriate medical treatment used to manage immediate allergic reactions must be immediately available in the event an anaphylactic reaction occurs following administration of ABRYSVO.

Syncope (fainting) may occur in association with administration of injectable vaccines, including ABRYSVO. Procedures should be in place to avoid injury from fainting.

Immunocompromised individuals, including those receiving immunosuppressive therapy, may have a diminished immune response to ABRYSVO.

Vaccination with ABRYSVO may not protect all vaccine recipients.

Because clinical trials are conducted under widely varying conditions, adverse reaction rates observed in the clinical trials of a vaccine cannot be directly compared to rates in the clinical trials of another vaccine and may not reflect the rates observed in practice.

Pregnant Individuals and Infants from Birth Through 6 Months of Age

The safety of ABRYSVO in maternal and infant participants was evaluated in two clinical studies in which approximately 4,000 maternal participants received a single dose of ABRYSVO.

Study 1 (NCT04424316) was a Phase 3, randomized, double-blind, multicenter, placebo-controlled study to investigate the efficacy and safety of ABRYSVO administered to pregnant individuals ≤49 years of age with uncomplicated, singleton pregnancies, to protect their infants against RSV disease. Pregnant individuals with high-risk pregnancies were excluded from the study (BMI>40 kg/m2 prior to pregnancy, pregnancies resulting after in vitro fertilization, preeclampsia, eclampsia, uncontrolled gestational hypertension, placental abnormalities, polyhydramnios or oligohydramnios, significant bleeding or blood clotting disorder, unstable endocrine disorders including untreated disorders of glucose intolerance or thyroid disorders). Pregnant individuals with prior pregnancy complications (e.g., history of preterm birth ≤34 weeks gestation, prior stillbirth, neonatal death, previous infant with a known genetic disorder or significant congenital anomaly) could be included, based on the investigators’ judgment, but were generally not enrolled in the study. In this study with 1:1 randomization 3,698 participants received ABRYSVO and 3,687 received placebo (0.5 mL dose, containing the same buffer ingredients in the same quantities as in a single dose of ABRYSVO [see Description (11)]). Infants born in year 1 were followed for up to 24 months, and infants born in year 2 were followed for up to 12 months to assess safety. At the time of final data evaluation, 3,659 infants were born to the maternal participants in the ABRYSVO group and 3,646 in the placebo group, and of these, approximately 93.3% have been followed for 12 months and 86.7% for 24 months. This multicenter study was conducted in Argentina, Australia, Brazil, Canada, Chile, Denmark, Finland, Gambia, Japan, Republic of Korea, Mexico, Netherlands, New Zealand, Philippines, South Africa, Spain, Taiwan, and the US.

Demographic characteristics in Study 1 among participants who received ABRYSVO and those who received placebo were generally similar with regard to age, race, and ethnicity. Of the participants in the study, 65% were White, 20% were Black or African American, 13% were Asian, and 29% were Hispanic/Latino. The median maternal age at the time of study vaccination was 29 years (range 16 to 45 years in the ABRYSVO group, 14 to 47 years in the placebo group). The median gestational age at vaccination was 31 weeks and 2 days (range 24-36.9 weeks). ABRYSVO is approved for use for pregnant individuals at 32 through 36 weeks gestational age [see Indications and Usage (1.1)]. The median infant gestational age at birth was 39 weeks and 1 day (range 27 weeks and 3 days to 44 weeks and 2 days). Among the infants born to maternal participants 51% were male and 49% were female.

Study 2 (NCT04032093) was a Phase 2, randomized, placebo-controlled, observer-blinded study that investigated the safety of two dose levels (120 mcg and a higher dose) of ABRYSVO administered to pregnant individuals. ABRYSVO (120 mcg) was administered to 115 maternal participants, and 114 infants were born to these maternal participants. This study was conducted in the US, South Africa, Argentina, and Chile. Demographic characteristics among participants who received ABRYSVO and those who received placebo were generally similar with regard to age, race, and ethnicity. Of the participants in the study, 76% were White, 21% were Black or African American, and 28% were Hispanic/Latino. The median age of participants was 27 years (range 18-42 years). The median gestational age at vaccination was 30 weeks (range 24-36 weeks). ABRYSVO is approved for use for pregnant individuals at 32 through 36 weeks gestational age [see Indications and Usage (1.1)].

For all maternal participants in Study 1, solicited local reactions and systemic events were collected using electronic diaries for 7 days after study vaccination, adverse events for 1 month and obstetric complications, serious adverse events, and adverse events of special interest for the duration of the study. For infant participants, the collection period for nonserious adverse events was from birth to 1 month. Serious adverse events were monitored for at least 1 year for all infant participants and for up to 2 years for half of the infants in Study 1.

Solicited Local and Systemic Reactions in Study 1

The majority of solicited local and systemic reactions in maternal participants resolved within 2-3 days of onset. Severe local reactions were reported for 0.3% of maternal participants in the ABRYSVO group and none in the placebo group, and severe systemic reactions within 7 days after vaccination were reported by 2.3% of maternal participants in both groups.

Solicited local and systemic reactions reported within 7 days after vaccination in Study 1 are presented in Tables 1 and 2.

<div class="scrollingtable"><table width="100%"> <caption> <span>Table 1     Percentage of Maternal Participants with Local Reactions Reported, by Maximum Severity, within 7 Days after Vaccination – Study 1<a class="Sup" href="#footnote-1" name="footnote-reference-1">*</a></span> </caption> <col width="27%"/> <col width="36%"/> <col width="37%"/> <tfoot> <tr class="First Last"> <td align="left" colspan="3" valign="top">Note: The presented results are based on the participants with solicited local reactogenicity data at the time of the data cut-off date for the primary analysis.</td> </tr> <tr> <td align="left" colspan="3"> <dl class="Footnote"> <dt> <a href="#footnote-reference-1" name="footnote-1">*</a> </dt> <dd>NCT04424316</dd> <dt> <a href="#footnote-reference-2" name="footnote-2">†</a> </dt> <dd>N = number of participants who provided e-diary data for a specific reaction after vaccination.</dd> <dt> <a href="#footnote-reference-3" name="footnote-3">‡</a> </dt> <dd>Mild: does not interfere with activity; moderate: interferes with activity; severe: prevents daily activity.</dd> <dt> <a href="#footnote-reference-4" name="footnote-4">§</a> </dt> <dd>Any includes all participants who reported a reaction as mild, moderate, or severe during Day 1 to Day 7 after vaccination.</dd> <dt> <a href="#footnote-reference-5" name="footnote-5">¶</a> </dt> <dd>Mild: &gt;2 cm to 5 cm; moderate: &gt;5 cm to 10 cm; severe: &gt;10 cm.</dd> </dl> </td> </tr> </tfoot> <tbody class="Headless"> <tr class="First"> <td align="center" class="Botrule Lrule Rrule Toprule" valign="top"> <p class="First"> <span class="Bold">Local Reactions</span> </p> </td><td align="center" class="Botrule Lrule Rrule Toprule" valign="top"> <p class="First"> <span class="Bold">ABRYSVO</span> </p> <p> <span class="Bold">N=3,663</span><a class="Sup" href="#footnote-2" name="footnote-reference-2">†</a> </p> <p> <span class="Bold">%</span> </p> </td><td align="center" class="Botrule Lrule Rrule Toprule" valign="top"> <p class="First"> <span class="Bold">PLACEBO</span> </p> <p> <span class="Bold">N=3,639</span><a class="Sup" href="#footnote-2">†</a> </p> <p> <span class="Bold">%</span> </p> </td> </tr> <tr> <td class="Botrule Lrule Rrule" colspan="3" valign="top"> <p class="First">Injection site pain<a class="Sup" href="#footnote-3" name="footnote-reference-3">‡</a> </p> </td> </tr> <tr> <td class="Botrule Lrule Rrule" valign="top"> <p class="First">     Any<a class="Sup" href="#footnote-4" name="footnote-reference-4">§</a> </p> </td><td align="center" class="Botrule Lrule Rrule Toprule" valign="top"> <p class="First">40.6</p> </td><td align="center" class="Botrule Lrule Rrule Toprule" valign="top"> <p class="First">10.1</p> </td> </tr> <tr> <td class="Botrule Lrule Rrule" valign="top"> <p class="First">     Mild</p> </td><td align="center" class="Botrule Lrule Rrule Toprule" valign="top"> <p class="First">36.1</p> </td><td align="center" class="Botrule Lrule Rrule Toprule" valign="top"> <p class="First">9.3</p> </td> </tr> <tr> <td class="Botrule Lrule Rrule" valign="top"> <p class="First">     Moderate</p> </td><td align="center" class="Botrule Lrule Rrule Toprule" valign="top"> <p class="First">4.4</p> </td><td align="center" class="Botrule Lrule Rrule Toprule" valign="top"> <p class="First">0.9</p> </td> </tr> <tr> <td class="Botrule Lrule Rrule" valign="top"> <p class="First">     Severe</p> </td><td align="center" class="Botrule Lrule Rrule Toprule" valign="top"> <p class="First">0.1</p> </td><td align="center" class="Botrule Lrule Rrule Toprule" valign="top"> <p class="First">0</p> </td> </tr> <tr> <td class="Botrule Lrule Rrule" colspan="3" valign="top"> <p class="First">Redness<a class="Sup" href="#footnote-5" name="footnote-reference-5">¶</a> </p> </td> </tr> <tr> <td class="Botrule Lrule Rrule" valign="top"> <p class="First">     Any<a class="Sup" href="#footnote-4">§</a> </p> </td><td align="center" class="Botrule Lrule Rrule Toprule" valign="top"> <p class="First">7.2</p> </td><td align="center" class="Botrule Lrule Rrule Toprule" valign="top"> <p class="First">0.2</p> </td> </tr> <tr> <td class="Botrule Lrule Rrule" valign="top"> <p class="First">     Mild</p> </td><td align="center" class="Botrule Lrule Rrule Toprule" valign="top"> <p class="First">5.0</p> </td><td align="center" class="Botrule Lrule Rrule Toprule" valign="top"> <p class="First">0.1</p> </td> </tr> <tr> <td class="Botrule Lrule Rrule" valign="top"> <p class="First">     Moderate</p> </td><td align="center" class="Botrule Lrule Rrule Toprule" valign="top"> <p class="First">2.1</p> </td><td align="center" class="Botrule Lrule Rrule Toprule" valign="top"> <p class="First">0.1</p> </td> </tr> <tr> <td class="Botrule Lrule Rrule" valign="top"> <p class="First">     Severe</p> </td><td align="center" class="Botrule Lrule Rrule Toprule" valign="top"> <p class="First">0.1</p> </td><td align="center" class="Botrule Lrule Rrule Toprule" valign="top"> <p class="First">0</p> </td> </tr> <tr> <td class="Botrule Lrule Rrule" colspan="3" valign="top"> <p class="First">Swelling<a class="Sup" href="#footnote-5">¶</a> </p> </td> </tr> <tr> <td class="Botrule Lrule Rrule" valign="top"> <p class="First">     Any<a class="Sup" href="#footnote-4">§</a> </p> </td><td align="center" class="Botrule Lrule Rrule Toprule" valign="top"> <p class="First">6.2</p> </td><td align="center" class="Botrule Lrule Rrule Toprule" valign="top"> <p class="First">0.2</p> </td> </tr> <tr> <td class="Botrule Lrule Rrule" valign="top"> <p class="First">     Mild</p> </td><td align="center" class="Botrule Lrule Rrule Toprule" valign="top"> <p class="First">4.1</p> </td><td align="center" class="Botrule Lrule Rrule Toprule" valign="top"> <p class="First">0.1</p> </td> </tr> <tr> <td class="Botrule Lrule Rrule" valign="top"> <p class="First">     Moderate</p> </td><td align="center" class="Botrule Lrule Rrule Toprule" valign="top"> <p class="First">2.0</p> </td><td align="center" class="Botrule Lrule Rrule Toprule" valign="top"> <p class="First">&lt;0.1</p> </td> </tr> <tr class="Last"> <td class="Botrule Lrule Rrule Toprule" valign="top"> <p class="First">     Severe</p> </td><td align="center" class="Botrule Lrule Rrule Toprule" valign="top"> <p class="First">&lt;0.1</p> </td><td align="center" class="Botrule Lrule Rrule Toprule" valign="top"> <p class="First">0</p> </td> </tr> </tbody> </table></div>

<div class="scrollingtable"><table width="100%"> <caption> <span>Table 2     Percentage of Maternal Participants with Systemic Reactions Reported, by Maximum Severity, within 7 Days after Vaccination – Study 1<a class="Sup" href="#footnote-6" name="footnote-reference-6">*</a></span> </caption> <col width="27%"/> <col width="36%"/> <col width="37%"/> <tfoot> <tr class="First Last"> <td align="left" colspan="3" valign="top">Note: The presented results are based on the participants with solicited systemic reactogenicity data at the time of the data cut-off date for the primary analysis.</td> </tr> <tr> <td align="left" colspan="3"> <dl class="Footnote"> <dt> <a href="#footnote-reference-6" name="footnote-6">*</a> </dt> <dd>NCT04424316</dd> <dt> <a href="#footnote-reference-7" name="footnote-7">†</a> </dt> <dd>N = number of participants who provided e-diary data for a specific reaction after vaccination. </dd> <dt> <a href="#footnote-reference-8" name="footnote-8">‡</a> </dt> <dd>Mild: does not interfere with activity; moderate: some interference with activity; severe: prevents daily routine activity.</dd> <dt> <a href="#footnote-reference-9" name="footnote-9">§</a> </dt> <dd>Any includes all participants who reported a reaction as mild, moderate, or severe during Day 1 to Day 7 after vaccination.</dd> <dt> <a href="#footnote-reference-10" name="footnote-10">¶</a> </dt> <dd>Mild: 2 to 3 loose stools in 24 hours; moderate: 4 to 5 loose stools in 24 hours; severe: 6 or more loose stools in 24 hours.</dd> <dt> <a href="#footnote-reference-11" name="footnote-11">#</a> </dt> <dd>Mild: 1 to 2 times in 24 hours; moderate: &gt;2 times in 24 hours; severe: requires intravenous hydration.</dd> </dl> </td> </tr> </tfoot> <tbody class="Headless"> <tr class="First"> <td align="center" class="Botrule Lrule Rrule Toprule" valign="top"> <p class="First"> <span class="Bold">Systemic Reactions</span> </p> </td><td align="center" class="Botrule Lrule Rrule Toprule" valign="top"> <p class="First"> <span class="Bold">ABRYSVO</span> </p> <p> <span class="Bold">N=3,663</span><a class="Sup" href="#footnote-7" name="footnote-reference-7">†</a> </p> <p> <span class="Bold">%</span> </p> </td><td align="center" class="Botrule Lrule Rrule Toprule" valign="top"> <p class="First"> <span class="Bold">PLACEBO</span> </p> <p> <span class="Bold">N=3,638-3,639</span><a class="Sup" href="#footnote-7">†</a> </p> <p> <span class="Bold">%</span> </p> </td> </tr> <tr> <td class="Botrule Lrule Rrule" colspan="3" valign="top"> <p class="First">Fever (≥38.0℃)</p> </td> </tr> <tr> <td class="Botrule Lrule Rrule" valign="top"> <p class="First">     ≥38.0°C</p> </td><td align="center" class="Botrule Lrule Rrule Toprule" valign="top"> <p class="First">2.6</p> </td><td align="center" class="Botrule Lrule Rrule Toprule" valign="top"> <p class="First">2.9</p> </td> </tr> <tr> <td class="Botrule Lrule Rrule" valign="top"> <p class="First">     ≥38.0°C to 38.4°C</p> </td><td align="center" class="Botrule Lrule Rrule Toprule" valign="top"> <p class="First">1.7</p> </td><td align="center" class="Botrule Lrule Rrule Toprule" valign="top"> <p class="First">1.5</p> </td> </tr> <tr> <td class="Botrule Lrule Rrule" valign="top"> <p class="First">     &gt;38.5°C to 38.9°C</p> </td><td align="center" class="Botrule Lrule Rrule Toprule" valign="top"> <p class="First">0.8</p> </td><td align="center" class="Botrule Lrule Rrule Toprule" valign="top"> <p class="First">1.2</p> </td> </tr> <tr> <td class="Botrule Lrule Rrule" valign="top"> <p class="First">     &gt;39.0°C to 40.0°C</p> </td><td align="center" class="Botrule Lrule Rrule Toprule" valign="top"> <p class="First">&lt;0.1</p> </td><td align="center" class="Botrule Lrule Rrule Toprule" valign="top"> <p class="First">0.1</p> </td> </tr> <tr> <td class="Botrule Lrule Rrule" valign="top"> <p class="First">     &gt;40.0°C</p> </td><td align="center" class="Botrule Lrule Rrule Toprule" valign="top"> <p class="First">&lt;0.1</p> </td><td align="center" class="Botrule Lrule Rrule Toprule" valign="top"> <p class="First">0.1</p> </td> </tr> <tr> <td class="Botrule Lrule Rrule" colspan="3" valign="top"> <p class="First">Fatigue<a class="Sup" href="#footnote-8" name="footnote-reference-8">‡</a> </p> </td> </tr> <tr> <td class="Botrule Lrule Rrule" valign="top"> <p class="First">     Any<a class="Sup" href="#footnote-9" name="footnote-reference-9">§</a> </p> </td><td align="center" class="Botrule Lrule Rrule Toprule" valign="top"> <p class="First">46.1</p> </td><td align="center" class="Botrule Lrule Rrule Toprule" valign="top"> <p class="First">43.8</p> </td> </tr> <tr> <td class="Botrule Lrule Rrule" valign="top"> <p class="First">     Mild</p> </td><td align="center" class="Botrule Lrule Rrule Toprule" valign="top"> <p class="First">23.4</p> </td><td align="center" class="Botrule Lrule Rrule Toprule" valign="top"> <p class="First">22.8</p> </td> </tr> <tr> <td class="Botrule Lrule Rrule" valign="top"> <p class="First">     Moderate</p> </td><td align="center" class="Botrule Lrule Rrule Toprule" valign="top"> <p class="First">21.4</p> </td><td align="center" class="Botrule Lrule Rrule Toprule" valign="top"> <p class="First">19.6</p> </td> </tr> <tr> <td class="Botrule Lrule Rrule" valign="top"> <p class="First">     Severe</p> </td><td align="center" class="Botrule Lrule Rrule Toprule" valign="top"> <p class="First">1.3</p> </td><td align="center" class="Botrule Lrule Rrule Toprule" valign="top"> <p class="First">1.4</p> </td> </tr> <tr> <td class="Botrule Lrule Rrule" colspan="3" valign="top"> <p class="First">Headache<a class="Sup" href="#footnote-8">‡</a> </p> </td> </tr> <tr> <td class="Botrule Lrule Rrule" valign="top"> <p class="First">     Any<a class="Sup" href="#footnote-9">§</a> </p> </td><td align="center" class="Botrule Lrule Rrule Toprule" valign="top"> <p class="First">31.0</p> </td><td align="center" class="Botrule Lrule Rrule Toprule" valign="top"> <p class="First">27.6</p> </td> </tr> <tr> <td class="Botrule Lrule Rrule" valign="top"> <p class="First">     Mild</p> </td><td align="center" class="Botrule Lrule Rrule Toprule" valign="top"> <p class="First">20.2</p> </td><td align="center" class="Botrule Lrule Rrule Toprule" valign="top"> <p class="First">17.9</p> </td> </tr> <tr> <td class="Botrule Lrule Rrule" valign="top"> <p class="First">     Moderate</p> </td><td align="center" class="Botrule Lrule Rrule Toprule" valign="top"> <p class="First">10.4</p> </td><td align="center" class="Botrule Lrule Rrule Toprule" valign="top"> <p class="First">9.3</p> </td> </tr> <tr> <td class="Botrule Lrule Rrule" valign="top"> <p class="First">     Severe</p> </td><td align="center" class="Botrule Lrule Rrule Toprule" valign="top"> <p class="First">0.4</p> </td><td align="center" class="Botrule Lrule Rrule Toprule" valign="top"> <p class="First">0.4</p> </td> </tr> <tr> <td class="Botrule Lrule Rrule" colspan="3" valign="top"> <p class="First">Muscle pain<a class="Sup" href="#footnote-8">‡</a> </p> </td> </tr> <tr> <td class="Botrule Lrule Rrule" valign="top"> <p class="First">     Any<a class="Sup" href="#footnote-9">§</a> </p> </td><td align="center" class="Botrule Lrule Rrule Toprule" valign="top"> <p class="First">26.5</p> </td><td align="center" class="Botrule Lrule Rrule Toprule" valign="top"> <p class="First">17.1</p> </td> </tr> <tr> <td class="Botrule Lrule Rrule" valign="top"> <p class="First">     Mild</p> </td><td align="center" class="Botrule Lrule Rrule Toprule" valign="top"> <p class="First">17.6</p> </td><td align="center" class="Botrule Lrule Rrule Toprule" valign="top"> <p class="First">10.0</p> </td> </tr> <tr> <td class="Botrule Lrule Rrule" valign="top"> <p class="First">     Moderate</p> </td><td align="center" class="Botrule Lrule Rrule Toprule" valign="top"> <p class="First">8.6</p> </td><td align="center" class="Botrule Lrule Rrule Toprule" valign="top"> <p class="First">6.8</p> </td> </tr> <tr> <td class="Botrule Lrule Rrule" valign="top"> <p class="First">     Severe</p> </td><td align="center" class="Botrule Lrule Rrule Toprule" valign="top"> <p class="First">0.4</p> </td><td align="center" class="Botrule Lrule Rrule Toprule" valign="top"> <p class="First">0.3</p> </td> </tr> <tr> <td class="Botrule Lrule Rrule" colspan="3" valign="top"> <p class="First">Nausea<a class="Sup" href="#footnote-8">‡</a> </p> </td> </tr> <tr> <td class="Botrule Lrule Rrule" valign="top"> <p class="First">     Any<a class="Sup" href="#footnote-9">§</a> </p> </td><td align="center" class="Botrule Lrule Rrule Toprule" valign="top"> <p class="First">20.0</p> </td><td align="center" class="Botrule Lrule Rrule Toprule" valign="top"> <p class="First">19.2</p> </td> </tr> <tr> <td class="Botrule Lrule Rrule" valign="top"> <p class="First">     Mild</p> </td><td align="center" class="Botrule Lrule Rrule Toprule" valign="top"> <p class="First">14.4</p> </td><td align="center" class="Botrule Lrule Rrule Toprule" valign="top"> <p class="First">13.8</p> </td> </tr> <tr> <td class="Botrule Lrule Rrule" valign="top"> <p class="First">     Moderate</p> </td><td align="center" class="Botrule Lrule Rrule Toprule" valign="top"> <p class="First">5.4</p> </td><td align="center" class="Botrule Lrule Rrule Toprule" valign="top"> <p class="First">5.2</p> </td> </tr> <tr> <td class="Botrule Lrule Rrule" valign="top"> <p class="First">     Severe</p> </td><td align="center" class="Botrule Lrule Rrule Toprule" valign="top"> <p class="First">0.2</p> </td><td align="center" class="Botrule Lrule Rrule Toprule" valign="top"> <p class="First">0.2</p> </td> </tr> <tr> <td class="Botrule Lrule Rrule" colspan="3" valign="top"> <p class="First">Joint pain<a class="Sup" href="#footnote-8">‡</a> </p> </td> </tr> <tr> <td class="Botrule Lrule Rrule" valign="top"> <p class="First">     Any<a class="Sup" href="#footnote-9">§</a> </p> </td><td align="center" class="Botrule Lrule Rrule Toprule" valign="top"> <p class="First">11.6</p> </td><td align="center" class="Botrule Lrule Rrule Toprule" valign="top"> <p class="First">10.5</p> </td> </tr> <tr> <td class="Botrule Lrule Rrule" valign="top"> <p class="First">     Mild</p> </td><td align="center" class="Botrule Lrule Rrule Toprule" valign="top"> <p class="First">6.5</p> </td><td align="center" class="Botrule Lrule Rrule Toprule" valign="top"> <p class="First">6.0</p> </td> </tr> <tr> <td class="Botrule Lrule Rrule" valign="top"> <p class="First">     Moderate</p> </td><td align="center" class="Botrule Lrule Rrule Toprule" valign="top"> <p class="First">4.9</p> </td><td align="center" class="Botrule Lrule Rrule Toprule" valign="top"> <p class="First">4.4</p> </td> </tr> <tr> <td class="Botrule Lrule Rrule" valign="top"> <p class="First">     Severe</p> </td><td align="center" class="Botrule Lrule Rrule Toprule" valign="top"> <p class="First">0.2</p> </td><td align="center" class="Botrule Lrule Rrule Toprule" valign="top"> <p class="First">&lt;0.1</p> </td> </tr> <tr> <td class="Botrule Lrule Rrule" colspan="3" valign="top"> <p class="First">Diarrhea<a class="Sup" href="#footnote-10" name="footnote-reference-10">¶</a> </p> </td> </tr> <tr> <td class="Botrule Lrule Rrule" valign="top"> <p class="First">     Any</p> </td><td align="center" class="Botrule Lrule Rrule Toprule" valign="top"> <p class="First">11.2</p> </td><td align="center" class="Botrule Lrule Rrule Toprule" valign="top"> <p class="First">11.5</p> </td> </tr> <tr> <td class="Botrule Lrule Rrule" valign="top"> <p class="First">     Mild</p> </td><td align="center" class="Botrule Lrule Rrule Toprule" valign="top"> <p class="First">9.1</p> </td><td align="center" class="Botrule Lrule Rrule Toprule" valign="top"> <p class="First">9.4</p> </td> </tr> <tr> <td class="Botrule Lrule Rrule" valign="top"> <p class="First">     Moderate</p> </td><td align="center" class="Botrule Lrule Rrule Toprule" valign="top"> <p class="First">2.0</p> </td><td align="center" class="Botrule Lrule Rrule Toprule" valign="top"> <p class="First">1.9</p> </td> </tr> <tr> <td class="Botrule Lrule Rrule" valign="top"> <p class="First">     Severe</p> </td><td align="center" class="Botrule Lrule Rrule Toprule" valign="top"> <p class="First">0.1</p> </td><td align="center" class="Botrule Lrule Rrule Toprule" valign="top"> <p class="First">0.2</p> </td> </tr> <tr> <td class="Botrule Lrule Rrule" colspan="3" valign="top"> <p class="First">Vomiting<a class="Sup" href="#footnote-11" name="footnote-reference-11">#</a> </p> </td> </tr> <tr> <td class="Botrule Lrule Rrule" valign="top"> <p class="First">     Any</p> </td><td align="center" class="Botrule Lrule Rrule Toprule" valign="top"> <p class="First">7.8</p> </td><td align="center" class="Botrule Lrule Rrule Toprule" valign="top"> <p class="First">7.0</p> </td> </tr> <tr> <td class="Botrule Lrule Rrule" valign="top"> <p class="First">     Mild</p> </td><td align="center" class="Botrule Lrule Rrule Toprule" valign="top"> <p class="First">6.4</p> </td><td align="center" class="Botrule Lrule Rrule Toprule" valign="top"> <p class="First">5.4</p> </td> </tr> <tr> <td class="Botrule Lrule Rrule" valign="top"> <p class="First">     Moderate</p> </td><td align="center" class="Botrule Lrule Rrule Toprule" valign="top"> <p class="First">1.3</p> </td><td align="center" class="Botrule Lrule Rrule Toprule" valign="top"> <p class="First">1.5</p> </td> </tr> <tr class="Last"> <td class="Botrule Lrule Rrule Toprule" valign="top"> <p class="First">     Severe</p> </td><td align="center" class="Botrule Lrule Rrule Toprule" valign="top"> <p class="First">0.2</p> </td><td align="center" class="Botrule Lrule Rrule Toprule" valign="top"> <p class="First">&lt;0.1</p> </td> </tr> </tbody> </table></div>

Unsolicited Adverse Events in Study 1

Unsolicited adverse events reported within 1 month after vaccination by maternal participants were 14.0% in the ABRYSVO group and 13.2% in the placebo group.

The most frequently reported unsolicited adverse events in maternal participants from vaccination through the 1-month follow-up visit were disorders of pregnancy, puerperium and perinatal conditions (7.0% for the ABRYSVO group versus 6.3% for the placebo group).

Serious Adverse Events in Study 1

In Study 1, serious adverse events in maternal participants were reported by 16.6% in the ABRYSVO group and 15.8% in the placebo group occurring any time during the study (see Table 3) with 4.3% serious adverse events in the ABRYSVO group and 3.8% in the placebo group occurring within 1 month after vaccination. Most of the serious adverse events in maternal participants were related to pregnancy complications and occurred after the 1 month period following vaccination.

<div class="scrollingtable"><table width="100%"> <caption> <span>Table 3     Select Pregnancy-related Serious Adverse Events in Study 1 in Pregnant Individuals Occurring at any Time Following Vaccination<a class="Sup" href="#footnote-12" name="footnote-reference-12">*</a></span> </caption> <col width="20%"/> <col width="20%"/> <col width="20%"/> <col width="20%"/> <col width="20%"/> <tfoot> <tr> <td align="left" colspan="5"> <dl class="Footnote"> <dt> <a href="#footnote-reference-12" name="footnote-12">*</a> </dt> <dd>Includes all SAEs from vaccination to 6 months post-delivery (up to approximately 10 months, depending on the gestational age at the time of vaccination). In Study 1, HELLP syndrome occurred in 5 participants (2 in the ABRYSVO group and 3 in the placebo group).</dd> <dt> <a href="#footnote-reference-13" name="footnote-13">†</a> </dt> <dd>There was one maternal death in the ABRYSVO group due to postpartum hemorrhage that was not likely to be associated with vaccination.</dd> <dt> <a href="#footnote-reference-14" name="footnote-14">‡</a> </dt> <dd>A total of 19 intrauterine deaths were reported for the index pregnancy: 10 intrauterine deaths in the ABRYSVO group (0.3%) and 9 intrauterine deaths in the placebo group (0.2%). The intrauterine deaths represented various clinical conditions and presentations resulting in fetal demise without clear evidence of a common pathophysiology.</dd> </dl> </td> </tr> </tfoot> <tbody class="Headless"> <tr class="First"> <td class="Botrule Lrule Rrule Toprule" valign="top"> <p class="First"> <span class="Bold">Serious Adverse Reaction</span> </p> </td><td align="center" class="Botrule Lrule Rrule Toprule" valign="top"> <p class="First"> <span class="Bold">ABRYSVO</span> </p> <p> <span class="Bold">N=3,698</span> </p> <p> <span class="Bold">n (%)</span> </p> </td><td align="center" class="Botrule Lrule Rrule Toprule" valign="top"> <p class="First"> <span class="Bold">95% CI</span> </p> </td><td align="center" class="Botrule Lrule Rrule Toprule" valign="top"> <p class="First"> <span class="Bold">Placebo</span> </p> <p> <span class="Bold">N=3,687</span> </p> <p> <span class="Bold">n (%)</span> </p> </td><td align="center" class="Botrule Lrule Rrule Toprule" valign="top"> <p class="First"> <span class="Bold">95% CI</span> </p> </td> </tr> <tr> <td class="Botrule Lrule Rrule" valign="top"> <p class="First">All Maternal SAEs</p> </td><td align="center" class="Botrule Lrule Rrule Toprule" valign="top"> <p class="First">613 (16.6)</p> </td><td align="center" class="Botrule Lrule Rrule Toprule" valign="top"> <p class="First">(15.4, 17.8)</p> </td><td align="center" class="Botrule Lrule Rrule Toprule" valign="top"> <p class="First">581 (15.8)</p> </td><td align="center" class="Botrule Lrule Rrule Toprule" valign="top"> <p class="First">(14.6, 17.0)</p> </td> </tr> <tr> <td class="Botrule Lrule Rrule" valign="top"> <p class="First">Pre-eclampsia</p> </td><td align="center" class="Botrule Lrule Rrule Toprule" valign="top"> <p class="First">67 (1.8)</p> </td><td align="center" class="Botrule Lrule Rrule Toprule" valign="top"> <p class="First">(1.4, 2.3)</p> </td><td align="center" class="Botrule Lrule Rrule Toprule" valign="top"> <p class="First">53 (1.4)</p> </td><td align="center" class="Botrule Lrule Rrule Toprule" valign="top"> <p class="First">(1.1, 1.9)</p> </td> </tr> <tr> <td class="Botrule Lrule Rrule" valign="top"> <p class="First">Gestational hypertension</p> </td><td align="center" class="Botrule Lrule Rrule Toprule" valign="top"> <p class="First">43 (1.2)</p> </td><td align="center" class="Botrule Lrule Rrule Toprule" valign="top"> <p class="First">(0.8, 1.6)</p> </td><td align="center" class="Botrule Lrule Rrule Toprule" valign="top"> <p class="First">41 (1.1)</p> </td><td align="center" class="Botrule Lrule Rrule Toprule" valign="top"> <p class="First">(0.8, 1.5)</p> </td> </tr> <tr> <td class="Botrule Lrule Rrule" valign="top"> <p class="First">Eclampsia</p> </td><td align="center" class="Botrule Lrule Rrule Toprule" valign="top"> <p class="First">7 (0.2)</p> </td><td align="center" class="Botrule Lrule Rrule Toprule" valign="top"> <p class="First">(0.1, 0.4)</p> </td><td align="center" class="Botrule Lrule Rrule Toprule" valign="top"> <p class="First">3 (&lt;0.1)</p> </td><td align="center" class="Botrule Lrule Rrule Toprule" valign="top"> <p class="First">(0.0, 0.2)</p> </td> </tr> <tr> <td class="Botrule Lrule Rrule" valign="top"> <p class="First">Premature rupture of membranes</p> </td><td align="center" class="Botrule Lrule Rrule Toprule" valign="top"> <p class="First">14 (0.4)</p> </td><td align="center" class="Botrule Lrule Rrule Toprule" valign="top"> <p class="First">(0.2, 0.6)</p> </td><td align="center" class="Botrule Lrule Rrule Toprule" valign="top"> <p class="First">16 (0.4)</p> </td><td align="center" class="Botrule Lrule Rrule Toprule" valign="top"> <p class="First">(0.2, 0.7)</p> </td> </tr> <tr> <td class="Botrule Lrule Rrule" valign="top"> <p class="First">Preterm premature rupture of membranes</p> </td><td align="center" class="Botrule Lrule Rrule Toprule" valign="top"> <p class="First">15 (0.4)</p> </td><td align="center" class="Botrule Lrule Rrule Toprule" valign="top"> <p class="First">(0.2, 0.7)</p> </td><td align="center" class="Botrule Lrule Rrule Toprule" valign="top"> <p class="First">11 (0.3)</p> </td><td align="center" class="Botrule Lrule Rrule Toprule" valign="top"> <p class="First">(0.1, 0.5)</p> </td> </tr> <tr> <td class="Botrule Lrule Rrule" valign="top"> <p class="First">Hypertension</p> </td><td align="center" class="Botrule Lrule Rrule Toprule" valign="top"> <p class="First">13 (0.4)</p> </td><td align="center" class="Botrule Lrule Rrule Toprule" valign="top"> <p class="First">(0.2, 0.6)</p> </td><td align="center" class="Botrule Lrule Rrule Toprule" valign="top"> <p class="First">6 (0.2)</p> </td><td align="center" class="Botrule Lrule Rrule Toprule" valign="top"> <p class="First">(0.1, 0.4)</p> </td> </tr> <tr> <td class="Botrule Lrule Rrule" valign="top"> <p class="First">Maternal death<a class="Sup" href="#footnote-13" name="footnote-reference-13">†</a> </p> </td><td align="center" class="Botrule Lrule Rrule Toprule" valign="top"> <p class="First">1 (&lt;0.1)</p> </td><td align="center" class="Botrule Lrule Rrule Toprule" valign="top"> <p class="First">(0.0, 0.2)</p> </td><td align="center" class="Botrule Lrule Rrule Toprule" valign="top"> <p class="First">0</p> </td><td align="center" class="Botrule Lrule Rrule Toprule" valign="top"> <p class="First">(0.0, 0.1)</p> </td> </tr> <tr class="Last"> <td class="Botrule Lrule Rrule Toprule" valign="top"> <p class="First">Fetal death<a class="Sup" href="#footnote-14" name="footnote-reference-14">‡</a> </p> </td><td align="center" class="Botrule Lrule Rrule Toprule" valign="top"> <p class="First">10 (0.3)</p> </td><td align="center" class="Botrule Lrule Rrule Toprule" valign="top"> <p class="First">(0.1, 0.5)</p> </td><td align="center" class="Botrule Lrule Rrule Toprule" valign="top"> <p class="First">9 (0.2)</p> </td><td align="center" class="Botrule Lrule Rrule Toprule" valign="top"> <p class="First">(0.1, 0.5)</p> </td> </tr> </tbody> </table></div>

Preterm Births in Study 1 and Study 2

A numerical imbalance in preterm births in ABRYSVO recipients compared to placebo recipients was observed in both Studies 1 and 2. In Study 2, preterm births occurred in 5.3% (6 out of 114) in the ABRYSVO group and 2.6% (3 out of 116) in the placebo group. In the subsequent Study 1, preterm birth events occurred in 5.7% [95% CI: 4.9, 6.5] (207 out of 3,659) in the ABRYSVO group and 4.7% [95% CI: 4.1, 5.5] (172 out of 3,646) in the placebo group. In infants born preterm, 84 infants in the ABRYSVO group and 81 infants in the placebo group remained hospitalized or were readmitted to the hospital in the neonatal period (up to 30 days after birth). Available data are insufficient to establish or exclude a causal relationship between preterm birth and ABRYSVO.

A numerical imbalance in preterm births was also observed in Study 1 among the subgroup of infants born to participants who were vaccinated at 32 through 36 weeks gestation, with 4.3% (71/1,667) in the ABRYSVO group and 3.7% (60/1,640) in the placebo group.

Adverse Reactions in Infants

In Study 1, adverse events in infants from birth to 1 month of age were observed in 38.0% in the ABRYSVO group compared to 35.4% in the placebo group. Low birth weight was observed in 5.1% of participants in the ABRYSVO group versus 4.3% in the placebo group, and neonatal jaundice was observed in 7.3% in the ABRYSVO group versus 6.9% in the placebo group.

Individuals 18 Years of Age and Older

Individuals 60 Years of Age and Older

The safety of ABRYSVO was evaluated in Study 3 (NCT05035212) in which 18,574 participants received ABRYSVO and 18,288 received placebo (0.5 mL dose, containing the same buffer ingredients in the same quantities as in a single dose of ABRYSVO [see Description (11)]). Study 3 was a multicenter, randomized, double-blind, placebo-controlled study to assess the efficacy and safety of ABRYSVO in individuals 60 years of age and older. This study was conducted in the US, Argentina, Japan, the Netherlands, Canada, South Africa, and Finland. Demographic characteristics among participants who received ABRYSVO and those who received placebo were generally similar with regard to age, sex, race, and ethnicity. Of the participants in the study, 51% were male and 80% were White, 12% were Black or African American, 7% were Asian, and 41% were Hispanic/Latino. The median age of participants was 67 years (range 59-97 years).

Solicited local and systemic reactions were collected using electronic diaries for 7 days after study vaccination in 7,116 participants (3,669 ABRYSVO participants and 3,447 placebo recipients) from a subset of sites. For all participants, unsolicited adverse events were collected for one month after study vaccination; serious adverse events (SAEs) are collected throughout study participation with a median duration of follow-up of 17.5 months.

Solicited Local and Systemic Reactions in Study 3

Solicited local and systemic reactions reported within 7 days after vaccination in Study 3 are presented in Tables 4 and 5.

<div class="scrollingtable"><table width="65%"> <caption> <span>Table 4     Percentage of Participants 60 Years of Age and Older with Local Reactions Reported, by Maximum Severity, within 7 Days after Vaccination – Study 3<a class="Sup" href="#footnote-15" name="footnote-reference-15">*</a></span> </caption> <col width="26%"/> <col width="25%"/> <col width="25%"/> <thead> <tr class="First Last"> <th align="left" class="Botrule Lrule Rrule Toprule" valign="top"><span class="Bold">Local Reactions</span></th><th align="center" class="Botrule Rrule Toprule" valign="top"><span class="Bold">ABRYSVO</span> <br/> <span class="Bold">N=3,628</span><a class="Sup" href="#footnote-16" name="footnote-reference-16">†</a> <br/> <span class="Bold">%</span></th><th align="center" class="Botrule Rrule Toprule" valign="top"><span class="Bold">PLACEBO</span> <br/> <span class="Bold">N=3,447</span><a class="Sup" href="#footnote-16">†</a> <br/> <span class="Bold">%</span></th> </tr> </thead> <tfoot> <tr> <td align="left" colspan="3"> <dl class="Footnote"> <dt> <a href="#footnote-reference-15" name="footnote-15">*</a> </dt> <dd>NCT05035212</dd> <dt> <a href="#footnote-reference-16" name="footnote-16">†</a> </dt> <dd>N = number of participants who provided e-diary data for a specific reaction after vaccination.</dd> <dt> <a href="#footnote-reference-17" name="footnote-17">‡</a> </dt> <dd>Mild: does not interfere with activity; moderate: some interference with activity; severe: prevents daily activity.</dd> <dt> <a href="#footnote-reference-18" name="footnote-18">§</a> </dt> <dd>Any includes all participants who reported a reaction as mild, moderate, or severe during Day 1 to Day 7 after vaccination.</dd> <dt> <a href="#footnote-reference-19" name="footnote-19">¶</a> </dt> <dd>Mild: 2.5 cm to 5 cm; moderate: &gt;5 cm to 10 cm; severe: &gt;10 cm (for data reported from e-diaries).</dd> </dl> </td> </tr> </tfoot> <tbody> <tr class="First"> <td class="Botrule Lrule Rrule Toprule" colspan="3" valign="top"> <p class="First">Injection site pain<a class="Sup" href="#footnote-17" name="footnote-reference-17">‡</a> </p> </td> </tr> <tr> <td class="Botrule Lrule Rrule" valign="top"> <p class="First">     Any<a class="Sup" href="#footnote-18" name="footnote-reference-18">§</a> </p> </td><td align="center" class="Botrule Rrule" valign="top"> <p class="First">10.6</p> </td><td align="center" class="Botrule Rrule" valign="top"> <p class="First">6.1</p> </td> </tr> <tr> <td class="Botrule Lrule Rrule" valign="top"> <p class="First">     Mild</p> </td><td align="center" class="Botrule Rrule" valign="top"> <p class="First">9.5</p> </td><td align="center" class="Botrule Rrule" valign="top"> <p class="First">5.4</p> </td> </tr> <tr> <td class="Botrule Lrule Rrule" valign="top"> <p class="First">     Moderate</p> </td><td align="center" class="Botrule Rrule" valign="top"> <p class="First">1.1</p> </td><td align="center" class="Botrule Rrule" valign="top"> <p class="First">0.7</p> </td> </tr> <tr> <td class="Botrule Lrule Rrule" valign="top"> <p class="First">     Severe</p> </td><td align="center" class="Botrule Rrule" valign="top"> <p class="First">&lt;0.1</p> </td><td align="center" class="Botrule Rrule" valign="top"> <p class="First">0</p> </td> </tr> <tr> <td class="Botrule Lrule Rrule" colspan="3" valign="top"> <p class="First">Redness<a class="Sup" href="#footnote-18">§</a><a class="Sup" href="#footnote-19" name="footnote-reference-19">¶</a> </p> </td> </tr> <tr> <td class="Botrule Lrule Rrule" valign="top"> <p class="First">     Any<a class="Sup" href="#footnote-18">§</a> </p> </td><td align="center" class="Botrule Rrule" valign="top"> <p class="First">2.7</p> </td><td align="center" class="Botrule Rrule" valign="top"> <p class="First">0.6</p> </td> </tr> <tr> <td class="Botrule Lrule Rrule" valign="top"> <p class="First">     Mild</p> </td><td align="center" class="Botrule Rrule" valign="top"> <p class="First">1.6</p> </td><td align="center" class="Botrule Rrule" valign="top"> <p class="First">0.4</p> </td> </tr> <tr> <td class="Botrule Lrule Rrule" valign="top"> <p class="First">     Moderate</p> </td><td align="center" class="Botrule Rrule" valign="top"> <p class="First">1.0</p> </td><td align="center" class="Botrule Rrule" valign="top"> <p class="First">0.2</p> </td> </tr> <tr> <td class="Botrule Lrule Rrule" valign="top"> <p class="First">     Severe</p> </td><td align="center" class="Botrule Rrule" valign="top"> <p class="First">0.1</p> </td><td align="center" class="Botrule Rrule" valign="top"> <p class="First">0</p> </td> </tr> <tr> <td class="Botrule Lrule Rrule" colspan="3" valign="top"> <p class="First">Swelling<a class="Sup" href="#footnote-18">§</a><a class="Sup" href="#footnote-19">¶</a> </p> </td> </tr> <tr> <td class="Botrule Lrule Rrule" valign="top"> <p class="First">     Any<a class="Sup" href="#footnote-18">§</a> </p> </td><td align="center" class="Botrule Rrule" valign="top"> <p class="First">2.5</p> </td><td align="center" class="Botrule Rrule" valign="top"> <p class="First">0.4</p> </td> </tr> <tr> <td class="Botrule Lrule Rrule" valign="top"> <p class="First">     Mild</p> </td><td align="center" class="Botrule Rrule" valign="top"> <p class="First">1.5</p> </td><td align="center" class="Botrule Rrule" valign="top"> <p class="First">0.2</p> </td> </tr> <tr> <td class="Botrule Lrule Rrule" valign="top"> <p class="First">     Moderate</p> </td><td align="center" class="Botrule Rrule" valign="top"> <p class="First">0.9</p> </td><td align="center" class="Botrule Rrule" valign="top"> <p class="First">0.1</p> </td> </tr> <tr class="Last"> <td class="Botrule Lrule Rrule" valign="top"> <p class="First">     Severe</p> </td><td align="center" class="Botrule Rrule" valign="top"> <p class="First">0.1</p> </td><td align="center" class="Botrule Rrule" valign="top"> <p class="First">&lt;0.1</p> </td> </tr> </tbody> </table></div>

<div class="scrollingtable"><table width="65%"> <caption> <span>Table 5     Percentage of Participants 60 Years of Age and Older with Systemic Reactions Reported, by Maximum Severity, within 7 Days after Vaccination – Study 3<a class="Sup" href="#footnote-20" name="footnote-reference-20">*</a></span> </caption> <col width="25%"/> <col width="25%"/> <col width="26%"/> <thead> <tr class="First Last"> <th align="left" class="Botrule Lrule Rrule Toprule" valign="top"><span class="Bold">Systemic Reactions</span></th><th align="center" class="Botrule Rrule Toprule" valign="top"><span class="Bold">ABRYSVO</span> <br/> <span class="Bold">N=3,628</span><a class="Sup" href="#footnote-21" name="footnote-reference-21">†</a> <br/> <span class="Bold">%</span></th><th align="center" class="Botrule Rrule Toprule" valign="top"><span class="Bold">PLACEBO</span> <br/> <span class="Bold">N=3,447</span><a class="Sup" href="#footnote-21">†</a> <br/> <span class="Bold">%</span></th> </tr> </thead> <tfoot> <tr> <td align="left" colspan="3"> <dl class="Footnote"> <dt> <a href="#footnote-reference-20" name="footnote-20">*</a> </dt> <dd>NCT05035212</dd> <dt> <a href="#footnote-reference-21" name="footnote-21">†</a> </dt> <dd>N = number of participants who provided e-diary data for a specific reaction after vaccination.</dd> <dt> <a href="#footnote-reference-22" name="footnote-22">‡</a> </dt> <dd>Mild: does not interfere with activity; moderate: some interference with activity; severe: prevents daily routine activity.</dd> <dt> <a href="#footnote-reference-23" name="footnote-23">§</a> </dt> <dd>Any includes all participants who reported a reaction as mild, moderate, or severe during Day 1 to Day 7 after vaccination.</dd> <dt> <a href="#footnote-reference-24" name="footnote-24">¶</a> </dt> <dd>Mild: 1 to 2 times in 24 hours; moderate: &gt;2 times in 24 hours; severe: requires intravenous hydration.</dd> <dt> <a href="#footnote-reference-25" name="footnote-25">#</a> </dt> <dd>Mild: 2 to 3 loose stools in 24 hours; moderate: 4 to 5 loose stools in 24 hours; severe: 6 or more loose stools in 24 hours.</dd> </dl> </td> </tr> </tfoot> <tbody> <tr class="First"> <td class="Botrule Lrule Rrule Toprule" colspan="3" valign="top"> <p class="First">Fever (≥38.0℃)</p> </td> </tr> <tr> <td class="Botrule Lrule Rrule" valign="top"> <p class="First">     ≥38.0°C</p> </td><td align="center" class="Botrule Rrule" valign="top"> <p class="First">1.4</p> </td><td align="center" class="Botrule Rrule" valign="top"> <p class="First">1.5</p> </td> </tr> <tr> <td class="Botrule Lrule Rrule" valign="top"> <p class="First">     ≥38.0°C to 38.4°C</p> </td><td align="center" class="Botrule Rrule" valign="top"> <p class="First">0.6</p> </td><td align="center" class="Botrule Rrule" valign="top"> <p class="First">0.8</p> </td> </tr> <tr> <td class="Botrule Lrule Rrule" valign="top"> <p class="First">     &gt;38.4°C to 38.9°C</p> </td><td align="center" class="Botrule Rrule" valign="top"> <p class="First">0.8</p> </td><td align="center" class="Botrule Rrule" valign="top"> <p class="First">0.6</p> </td> </tr> <tr> <td class="Botrule Lrule Rrule" valign="top"> <p class="First">     &gt;38.9°C to 40.0°C</p> </td><td align="center" class="Botrule Rrule" valign="top"> <p class="First">&lt;0.1</p> </td><td align="center" class="Botrule Rrule" valign="top"> <p class="First">&lt;0.1</p> </td> </tr> <tr> <td class="Botrule Lrule Rrule" valign="top"> <p class="First">     &gt;40.0°C</p> </td><td align="center" class="Botrule Rrule" valign="top"> <p class="First">0</p> </td><td align="center" class="Botrule Rrule" valign="top"> <p class="First">&lt;0.1</p> </td> </tr> <tr> <td class="Botrule Lrule Rrule" colspan="3" valign="top"> <p class="First">Fatigue<a class="Sup" href="#footnote-22" name="footnote-reference-22">‡</a> </p> </td> </tr> <tr> <td class="Botrule Lrule Rrule" valign="top"> <p class="First">     Any<a class="Sup" href="#footnote-23" name="footnote-reference-23">§</a> </p> </td><td align="center" class="Botrule Rrule" valign="top"> <p class="First">15.7</p> </td><td align="center" class="Botrule Rrule" valign="top"> <p class="First">14.8</p> </td> </tr> <tr> <td class="Botrule Lrule Rrule" valign="top"> <p class="First">     Mild</p> </td><td align="center" class="Botrule Rrule" valign="top"> <p class="First">9.3</p> </td><td align="center" class="Botrule Rrule" valign="top"> <p class="First">8.6</p> </td> </tr> <tr> <td class="Botrule Lrule Rrule" valign="top"> <p class="First">     Moderate</p> </td><td align="center" class="Botrule Rrule" valign="top"> <p class="First">6.0</p> </td><td align="center" class="Botrule Rrule" valign="top"> <p class="First">6.0</p> </td> </tr> <tr> <td class="Botrule Lrule Rrule" valign="top"> <p class="First">     Severe</p> </td><td align="center" class="Botrule Rrule" valign="top"> <p class="First">0.3</p> </td><td align="center" class="Botrule Rrule" valign="top"> <p class="First">0.1</p> </td> </tr> <tr> <td class="Botrule Lrule Rrule" colspan="3" valign="top"> <p class="First">Headache<a class="Sup" href="#footnote-22">‡</a> </p> </td> </tr> <tr> <td class="Botrule Lrule Rrule" valign="top"> <p class="First">     Any<a class="Sup" href="#footnote-23">§</a> </p> </td><td align="center" class="Botrule Rrule" valign="top"> <p class="First">12.9</p> </td><td align="center" class="Botrule Rrule" valign="top"> <p class="First">12.0</p> </td> </tr> <tr> <td class="Botrule Lrule Rrule" valign="top"> <p class="First">     Mild</p> </td><td align="center" class="Botrule Rrule" valign="top"> <p class="First">9.0</p> </td><td align="center" class="Botrule Rrule" valign="top"> <p class="First">8.6</p> </td> </tr> <tr> <td class="Botrule Lrule Rrule" valign="top"> <p class="First">     Moderate</p> </td><td align="center" class="Botrule Rrule" valign="top"> <p class="First">3.8</p> </td><td align="center" class="Botrule Rrule" valign="top"> <p class="First">3.2</p> </td> </tr> <tr> <td class="Botrule Lrule Rrule" valign="top"> <p class="First">     Severe</p> </td><td align="center" class="Botrule Rrule" valign="top"> <p class="First">0.1</p> </td><td align="center" class="Botrule Rrule" valign="top"> <p class="First">&lt;0.1</p> </td> </tr> <tr> <td class="Botrule Lrule Rrule" colspan="3" valign="top"> <p class="First">Muscle pain<a class="Sup" href="#footnote-22">‡</a> </p> </td> </tr> <tr> <td class="Botrule Lrule Rrule" valign="top"> <p class="First">     Any<a class="Sup" href="#footnote-23">§</a> </p> </td><td align="center" class="Botrule Rrule" valign="top"> <p class="First">10.2</p> </td><td align="center" class="Botrule Rrule" valign="top"> <p class="First">8.5</p> </td> </tr> <tr> <td class="Botrule Lrule Rrule" valign="top"> <p class="First">     Mild</p> </td><td align="center" class="Botrule Rrule" valign="top"> <p class="First">6.5</p> </td><td align="center" class="Botrule Rrule" valign="top"> <p class="First">5.6</p> </td> </tr> <tr> <td class="Botrule Lrule Rrule" valign="top"> <p class="First">     Moderate</p> </td><td align="center" class="Botrule Rrule" valign="top"> <p class="First">3.5</p> </td><td align="center" class="Botrule Rrule" valign="top"> <p class="First">2.8</p> </td> </tr> <tr> <td class="Botrule Lrule Rrule" valign="top"> <p class="First">     Severe</p> </td><td align="center" class="Botrule Rrule" valign="top"> <p class="First">0.2</p> </td><td align="center" class="Botrule Rrule" valign="top"> <p class="First">&lt;0.1</p> </td> </tr> <tr> <td class="Botrule Lrule Rrule" colspan="3" valign="top"> <p class="First">Joint pain<a class="Sup" href="#footnote-22">‡</a> </p> </td> </tr> <tr> <td class="Botrule Lrule Rrule" valign="top"> <p class="First">     Any<a class="Sup" href="#footnote-23">§</a> </p> </td><td align="center" class="Botrule Rrule" valign="top"> <p class="First">7.6</p> </td><td align="center" class="Botrule Rrule" valign="top"> <p class="First">7.0</p> </td> </tr> <tr> <td class="Botrule Lrule Rrule" valign="top"> <p class="First">     Mild</p> </td><td align="center" class="Botrule Rrule" valign="top"> <p class="First">4.5</p> </td><td align="center" class="Botrule Rrule" valign="top"> <p class="First">3.9</p> </td> </tr> <tr> <td class="Botrule Lrule Rrule" valign="top"> <p class="First">     Moderate</p> </td><td align="center" class="Botrule Rrule" valign="top"> <p class="First">3.0</p> </td><td align="center" class="Botrule Rrule" valign="top"> <p class="First">3.0</p> </td> </tr> <tr> <td class="Botrule Lrule Rrule" valign="top"> <p class="First">     Severe</p> </td><td align="center" class="Botrule Rrule" valign="top"> <p class="First">&lt;0.1</p> </td><td align="center" class="Botrule Rrule" valign="top"> <p class="First">&lt;0.1</p> </td> </tr> <tr> <td class="Botrule Lrule Rrule" colspan="3" valign="top"> <p class="First">Nausea<a class="Sup" href="#footnote-22">‡</a> </p> </td> </tr> <tr> <td class="Botrule Lrule Rrule" valign="top"> <p class="First">     Any<a class="Sup" href="#footnote-23">§</a> </p> </td><td align="center" class="Botrule Rrule" valign="top"> <p class="First">3.5</p> </td><td align="center" class="Botrule Rrule" valign="top"> <p class="First">3.8</p> </td> </tr> <tr> <td class="Botrule Lrule Rrule" valign="top"> <p class="First">     Mild</p> </td><td align="center" class="Botrule Rrule" valign="top"> <p class="First">2.6</p> </td><td align="center" class="Botrule Rrule" valign="top"> <p class="First">3.1</p> </td> </tr> <tr> <td class="Botrule Lrule Rrule" valign="top"> <p class="First">     Moderate</p> </td><td align="center" class="Botrule Rrule" valign="top"> <p class="First">0.9</p> </td><td align="center" class="Botrule Rrule" valign="top"> <p class="First">0.6</p> </td> </tr> <tr> <td class="Botrule Lrule Rrule" valign="top"> <p class="First">     Severe</p> </td><td align="center" class="Botrule Rrule" valign="top"> <p class="First">0</p> </td><td align="center" class="Botrule Rrule" valign="top"> <p class="First">&lt;0.1</p> </td> </tr> <tr> <td class="Botrule Lrule Rrule" colspan="3" valign="top"> <p class="First">Vomiting<a class="Sup" href="#footnote-24" name="footnote-reference-24">¶</a> </p> </td> </tr> <tr> <td class="Botrule Lrule Rrule" valign="top"> <p class="First">     Any<a class="Sup" href="#footnote-23">§</a> </p> </td><td align="center" class="Botrule Rrule" valign="top"> <p class="First">0.9</p> </td><td align="center" class="Botrule Rrule" valign="top"> <p class="First">0.9</p> </td> </tr> <tr> <td class="Botrule Lrule Rrule" valign="top"> <p class="First">     Mild</p> </td><td align="center" class="Botrule Rrule" valign="top"> <p class="First">0.7</p> </td><td align="center" class="Botrule Rrule" valign="top"> <p class="First">0.7</p> </td> </tr> <tr> <td class="Botrule Lrule Rrule" valign="top"> <p class="First">     Moderate</p> </td><td align="center" class="Botrule Rrule" valign="top"> <p class="First">0.2</p> </td><td align="center" class="Botrule Rrule" valign="top"> <p class="First">0.2</p> </td> </tr> <tr> <td class="Botrule Lrule Rrule" valign="top"> <p class="First">     Severe</p> </td><td align="center" class="Botrule Rrule" valign="top"> <p class="First">0</p> </td><td align="center" class="Botrule Rrule" valign="top"> <p class="First">&lt;0.1</p> </td> </tr> <tr> <td class="Botrule Lrule Rrule" colspan="3" valign="top"> <p class="First">Diarrhea<a class="Sup" href="#footnote-25" name="footnote-reference-25">#</a> </p> </td> </tr> <tr> <td class="Botrule Lrule Rrule" valign="top"> <p class="First">     Any<a class="Sup" href="#footnote-23">§</a> </p> </td><td align="center" class="Botrule Rrule" valign="top"> <p class="First">6.0</p> </td><td align="center" class="Botrule Rrule" valign="top"> <p class="First">5.3</p> </td> </tr> <tr> <td class="Botrule Lrule Rrule" valign="top"> <p class="First">     Mild</p> </td><td align="center" class="Botrule Rrule" valign="top"> <p class="First">4.5</p> </td><td align="center" class="Botrule Rrule" valign="top"> <p class="First">4.3</p> </td> </tr> <tr> <td class="Botrule Lrule Rrule" valign="top"> <p class="First">     Moderate</p> </td><td align="center" class="Botrule Rrule" valign="top"> <p class="First">1.4</p> </td><td align="center" class="Botrule Rrule" valign="top"> <p class="First">0.9</p> </td> </tr> <tr class="Last"> <td class="Botrule Lrule Rrule" valign="top"> <p class="First">     Severe</p> </td><td align="center" class="Botrule Rrule" valign="top"> <p class="First">0.1</p> </td><td align="center" class="Botrule Rrule" valign="top"> <p class="First">0.1</p> </td> </tr> </tbody> </table></div>

Solicited local and systemic reactions had a median duration of 1-2 days.

Unsolicited Adverse Events in Study 3

Unsolicited adverse events occurring within 1 month after vaccination were similar between groups, reported in 10.8% and 10.5% of participants who received ABRYSVO and placebo, respectively.

Within 30 days after vaccination, atrial fibrillation was reported in 11 vaccine recipients and 3 placebo recipients (of which 5 in the ABRYSVO group and 2 in the placebo group were serious adverse events); the onset of symptoms was 18 to 30 days post vaccination. The currently available information on atrial fibrillation is insufficient to determine a causal relationship to the vaccine. There were no other notable patterns or numerical imbalances between groups for specific categories of unsolicited adverse events.

Serious Adverse Events in Study 3

In Study 3, SAEs were reported by 6.2% of participants in the ABRYSVO group and 6.1% in the placebo group. Three participants in the ABRYSVO group had SAEs which were assessed as possibly related to study vaccination: Guillain‑Barré syndrome reported 7 days after vaccination (with diagnosis later revised to chronic inflammatory demyelinating polyneuropathy), Miller Fisher syndrome reported 8 days after vaccination, and hypersensitivity reported 8 hours after vaccination.

Individuals 18 through 59 Years of Age Considered to be at Increased Risk of LRTD caused by RSV

The safety of ABRYSVO was evaluated in Study 4 (NCT05842967) in which 453 participants received ABRYSVO and 225 received placebo (0.5 mL dose, containing the same buffer ingredients in the same quantities as in a single dose of ABRYSVO [see Description (11)]). Study 4 was a multicenter, randomized, double-blind, placebo-controlled study to assess the safety and immunogenicity of ABRYSVO in individuals 18 through 59 years of age considered to be at increased risk of LRTD caused by RSV due to certain chronic medical conditions [see Clinical Studies (14.3)]. This study was conducted in the US. Demographic characteristics among individuals who received ABRYSVO and those who received placebo were generally similar with regard to age, race, and ethnicity; 43% and 32% of participants in the ABRYSVO and placebo groups, respectively, were male. Of the participants in the study, 68% were White, 24% were Black or African American, 5% were Asian, and 22% were Hispanic/Latino. Fifty-two percent (52%) were 18 to 49 years and 48% were 50 to 59 years. The median age of participants was 49 years. The vaccine and placebo groups were similar with regard to the prevalence of underlying medical conditions: one or more chronic pulmonary condition (52%), diabetes (43%), one or more other disease (liver, renal, neurologic, hematologic, or other metabolic disease) (31%), and one or more cardiovascular condition (8%).

Solicited local and systemic adverse reactions that occurred within 7 days following study vaccination were self‑reported in electronic diaries or were reported to an investigator. Unsolicited adverse events were collected for 1 month after study vaccination; serious adverse events (SAEs) were collected for 6 months after study vaccination.

Solicited Local and Systemic Reactions in Study 4

Solicited local and systemic reactions reported within 7 days after vaccination in Study 4 are presented in Tables 6 and 7.

<div class="scrollingtable"><table class="Noautorules" width="100%"> <caption> <span>Table 6     Percentage of Participants 18 through 59 Years of Age at Increased Risk of LRTD caused by RSV with Local Reactions Reported, by Maximum Severity, within 7 Days after Vaccination – Study 4<a class="Sup" href="#footnote-26" name="footnote-reference-26">*</a></span> </caption> <col width="33%"/> <col width="33%"/> <col width="33%"/> <tfoot> <tr> <td align="left" colspan="3"> <dl class="Footnote"> <dt> <a href="#footnote-reference-26" name="footnote-26">*</a> </dt> <dd>NCT05842967</dd> <dt> <a href="#footnote-reference-27" name="footnote-27">†</a> </dt> <dd>N = number of participants reporting at least one response in the e-diary.</dd> <dt> <a href="#footnote-reference-28" name="footnote-28">‡</a> </dt> <dd>Mild: does not interfere with activity; moderate: some interference with activity; severe: prevents daily activity.</dd> <dt> <a href="#footnote-reference-29" name="footnote-29">§</a> </dt> <dd>Any includes all participants who reported a reaction as mild, moderate, or severe during Day 1 to Day 7 after vaccination.</dd> <dt> <a href="#footnote-reference-30" name="footnote-30">¶</a> </dt> <dd>Mild: &gt;2 cm to 5 cm; moderate: &gt;5 cm to 10 cm; severe: &gt;10 cm (for data reported from e-diaries).</dd> </dl> </td> </tr> </tfoot> <tbody class="Headless"> <tr> <td class="Botrule Lrule Rrule Toprule" valign="top"> <p class="First"> <span class="Bold">Local Reactions</span> </p> </td><td align="center" class="Botrule Lrule Rrule Toprule" valign="top"> <p class="First"> <span class="Bold">ABRYSVO</span> </p> <p> <span class="Bold">N=451<a class="Sup" href="#footnote-27" name="footnote-reference-27">†</a></span> </p> <p> <span class="Bold">%</span> </p> </td><td align="center" class="Botrule Lrule Rrule Toprule" valign="top"> <p class="First"> <span class="Bold">PLACEBO</span> </p> <p> <span class="Bold">N=225<a class="Sup" href="#footnote-27">†</a></span> </p> <p> <span class="Bold">%</span> </p> </td> </tr> <tr> <td class="Botrule Lrule Rrule" colspan="3" valign="top"> <p class="First">Injection site pain<a class="Sup" href="#footnote-28" name="footnote-reference-28">‡</a> </p> </td> </tr> <tr> <td class="Botrule Lrule Rrule" valign="top"> <p class="First">   Any<a class="Sup" href="#footnote-29" name="footnote-reference-29">§</a> </p> </td><td align="center" class="Botrule Lrule Rrule Toprule" valign="top"> <p class="First">35.3</p> </td><td align="center" class="Botrule Lrule Rrule Toprule" valign="top"> <p class="First">10.7</p> </td> </tr> <tr> <td class="Botrule Lrule Rrule" valign="top"> <p class="First">   Mild</p> </td><td align="center" class="Botrule Lrule Rrule Toprule" valign="top"> <p class="First">29.7</p> </td><td align="center" class="Botrule Lrule Rrule Toprule" valign="top"> <p class="First">10.2</p> </td> </tr> <tr> <td class="Botrule Lrule Rrule" valign="top"> <p class="First">   Moderate</p> </td><td align="center" class="Botrule Lrule Rrule Toprule" valign="top"> <p class="First">5.5</p> </td><td align="center" class="Botrule Lrule Rrule Toprule" valign="top"> <p class="First">0.4</p> </td> </tr> <tr> <td class="Botrule Lrule Rrule" valign="top"> <p class="First">   Severe</p> </td><td align="center" class="Botrule Lrule Rrule Toprule" valign="top"> <p class="First">0</p> </td><td align="center" class="Botrule Lrule Rrule Toprule" valign="top"> <p class="First">0</p> </td> </tr> <tr> <td class="Botrule Lrule Rrule" colspan="3" valign="top"> <p class="First">Redness<a class="Sup" href="#footnote-30" name="footnote-reference-30">¶</a> </p> </td> </tr> <tr> <td class="Botrule Lrule Rrule" valign="top"> <p class="First">   Any<a class="Sup" href="#footnote-29">§</a> </p> </td><td align="center" class="Botrule Lrule Rrule Toprule" valign="top"> <p class="First">6.0</p> </td><td align="center" class="Botrule Lrule Rrule Toprule" valign="top"> <p class="First">0.4</p> </td> </tr> <tr> <td class="Botrule Lrule Rrule" valign="top"> <p class="First">   Mild</p> </td><td align="center" class="Botrule Lrule Rrule Toprule" valign="top"> <p class="First">3.8</p> </td><td align="center" class="Botrule Lrule Rrule Toprule" valign="top"> <p class="First">0</p> </td> </tr> <tr> <td class="Botrule Lrule Rrule" valign="top"> <p class="First">   Moderate</p> </td><td align="center" class="Botrule Lrule Rrule Toprule" valign="top"> <p class="First">2.2</p> </td><td align="center" class="Botrule Lrule Rrule Toprule" valign="top"> <p class="First">0.4</p> </td> </tr> <tr> <td class="Botrule Lrule Rrule" valign="top"> <p class="First">   Severe</p> </td><td align="center" class="Botrule Lrule Rrule Toprule" valign="top"> <p class="First">0</p> </td><td align="center" class="Botrule Lrule Rrule Toprule" valign="top"> <p class="First">0</p> </td> </tr> <tr> <td class="Botrule Lrule Rrule" colspan="3" valign="top"> <p class="First">Swelling<a class="Sup" href="#footnote-30">¶</a> </p> </td> </tr> <tr> <td class="Botrule Lrule Rrule" valign="top"> <p class="First">   Any<a class="Sup" href="#footnote-29">§</a> </p> </td><td align="center" class="Botrule Lrule Rrule Toprule" valign="top"> <p class="First">7.1</p> </td><td align="center" class="Botrule Lrule Rrule Toprule" valign="top"> <p class="First">0.9</p> </td> </tr> <tr> <td class="Botrule Lrule Rrule" valign="top"> <p class="First">   Mild</p> </td><td align="center" class="Botrule Lrule Rrule Toprule" valign="top"> <p class="First">4.0</p> </td><td align="center" class="Botrule Lrule Rrule Toprule" valign="top"> <p class="First">0.4</p> </td> </tr> <tr> <td class="Botrule Lrule Rrule" valign="top"> <p class="First">   Moderate</p> </td><td align="center" class="Botrule Lrule Rrule Toprule" valign="top"> <p class="First">2.9</p> </td><td align="center" class="Botrule Lrule Rrule Toprule" valign="top"> <p class="First">0.4</p> </td> </tr> <tr> <td class="Botrule Lrule Rrule Toprule" valign="top"> <p class="First">   Severe</p> </td><td align="center" class="Botrule Lrule Rrule Toprule" valign="top"> <p class="First">0.2</p> </td><td align="center" class="Botrule Lrule Rrule Toprule" valign="top"> <p class="First">0</p> </td> </tr> </tbody> </table></div>

<div class="scrollingtable"><table class="Noautorules" width="100%"> <caption> <span>Table 7     Percentage of Participants 18 through 59 Years of Age at Increased Risk of LRTD caused by RSV with Systemic Reactions Reported, by Maximum Severity, within 7 Days after Vaccination – Study 4<a class="Sup" href="#footnote-31" name="footnote-reference-31">*</a></span> </caption> <col width="33%"/> <col width="33%"/> <col width="33%"/> <tfoot> <tr> <td align="left" colspan="3"> <dl class="Footnote"> <dt> <a href="#footnote-reference-31" name="footnote-31">*</a> </dt> <dd>NCT05842967</dd> <dt> <a href="#footnote-reference-32" name="footnote-32">†</a> </dt> <dd>N = number of participants reporting at least one response in the e-diary.</dd> <dt> <a href="#footnote-reference-33" name="footnote-33">‡</a> </dt> <dd>Mild: does not interfere with activity; moderate: some interference with activity; severe: prevents daily routine activity.</dd> <dt> <a href="#footnote-reference-34" name="footnote-34">§</a> </dt> <dd>Any includes all participants who reported a reaction as mild, moderate, or severe during Day 1 to Day 7 after vaccination.</dd> <dt> <a href="#footnote-reference-35" name="footnote-35">¶</a> </dt> <dd>Mild: 1 to 2 times in 24 hours; moderate: &gt;2 times in 24 hours; severe: requires intravenous hydration.</dd> <dt> <a href="#footnote-reference-36" name="footnote-36">#</a> </dt> <dd>Mild: 2 to 3 loose stools in 24 hours; moderate: 4 to 5 loose stools in 24 hours; severe: 6 or more loose stools in 24 hours.</dd> </dl> </td> </tr> </tfoot> <tbody class="Headless"> <tr> <td class="Botrule Lrule Rrule Toprule" valign="top"> <p class="First"> <span class="Bold">Systemic Reactions</span> </p> </td><td align="center" class="Botrule Lrule Rrule Toprule" valign="top"> <p class="First"> <span class="Bold">ABRYSVO</span> </p> <p> <span class="Bold">N=451</span><a class="Sup" href="#footnote-32" name="footnote-reference-32">†</a> </p> <p> <span class="Bold">%</span> </p> </td><td align="center" class="Botrule Lrule Rrule Toprule" valign="top"> <p class="First"> <span class="Bold">PLACEBO</span> </p> <p> <span class="Bold">N=225</span><a class="Sup" href="#footnote-32">†</a> </p> <p> <span class="Bold">%</span> </p> </td> </tr> <tr> <td class="Botrule Lrule Rrule" colspan="3" valign="top"> <p class="First">Fever (≥38.0℃)</p> </td> </tr> <tr> <td class="Botrule Lrule Rrule" valign="top"> <p class="First">   ≥38.0°C</p> </td><td align="center" class="Botrule Lrule Rrule Toprule" valign="top"> <p class="First">1.6</p> </td><td align="center" class="Botrule Lrule Rrule Toprule" valign="top"> <p class="First">1.3</p> </td> </tr> <tr> <td class="Botrule Lrule Rrule" valign="top"> <p class="First">   ≥38.0°C to 38.4°C</p> </td><td align="center" class="Botrule Lrule Rrule Toprule" valign="top"> <p class="First">0.4</p> </td><td align="center" class="Botrule Lrule Rrule Toprule" valign="top"> <p class="First">0.4</p> </td> </tr> <tr> <td class="Botrule Lrule Rrule" valign="top"> <p class="First">   &gt;38.4°C to 38.9°C</p> </td><td align="center" class="Botrule Lrule Rrule Toprule" valign="top"> <p class="First">1.1</p> </td><td align="center" class="Botrule Lrule Rrule Toprule" valign="top"> <p class="First">0.9</p> </td> </tr> <tr> <td class="Botrule Lrule Rrule" valign="top"> <p class="First">   &gt;38.9°C to 40.0°C</p> </td><td align="center" class="Botrule Lrule Rrule Toprule" valign="top"> <p class="First">0</p> </td><td align="center" class="Botrule Lrule Rrule Toprule" valign="top"> <p class="First">0</p> </td> </tr> <tr> <td class="Botrule Lrule Rrule" colspan="3" valign="top"> <p class="First">Fatigue<a class="Sup" href="#footnote-33" name="footnote-reference-33">‡</a> </p> </td> </tr> <tr> <td class="Botrule Lrule Rrule" valign="top"> <p class="First">   Any<a class="Sup" href="#footnote-34" name="footnote-reference-34">§</a> </p> </td><td align="center" class="Botrule Lrule Rrule Toprule" valign="top"> <p class="First">37.3</p> </td><td align="center" class="Botrule Lrule Rrule Toprule" valign="top"> <p class="First">38.2</p> </td> </tr> <tr> <td class="Botrule Lrule Rrule" valign="top"> <p class="First">   Mild</p> </td><td align="center" class="Botrule Lrule Rrule Toprule" valign="top"> <p class="First">18.2</p> </td><td align="center" class="Botrule Lrule Rrule Toprule" valign="top"> <p class="First">22.2</p> </td> </tr> <tr> <td class="Botrule Lrule Rrule" valign="top"> <p class="First">   Moderate</p> </td><td align="center" class="Botrule Lrule Rrule Toprule" valign="top"> <p class="First">18.2</p> </td><td align="center" class="Botrule Lrule Rrule Toprule" valign="top"> <p class="First">15.6</p> </td> </tr> <tr> <td class="Botrule Lrule Rrule" valign="top"> <p class="First">   Severe</p> </td><td align="center" class="Botrule Lrule Rrule Toprule" valign="top"> <p class="First">0.9</p> </td><td align="center" class="Botrule Lrule Rrule Toprule" valign="top"> <p class="First">0.4</p> </td> </tr> <tr> <td class="Botrule Lrule Rrule" colspan="3" valign="top"> <p class="First">Headache<a class="Sup" href="#footnote-33">‡</a> </p> </td> </tr> <tr> <td class="Botrule Lrule Rrule" valign="top"> <p class="First">   Any<a class="Sup" href="#footnote-34">§</a> </p> </td><td align="center" class="Botrule Lrule Rrule Toprule" valign="top"> <p class="First">28.4</p> </td><td align="center" class="Botrule Lrule Rrule Toprule" valign="top"> <p class="First">30.2</p> </td> </tr> <tr> <td class="Botrule Lrule Rrule" valign="top"> <p class="First">   Mild</p> </td><td align="center" class="Botrule Lrule Rrule Toprule" valign="top"> <p class="First">20.8</p> </td><td align="center" class="Botrule Lrule Rrule Toprule" valign="top"> <p class="First">18.7</p> </td> </tr> <tr> <td class="Botrule Lrule Rrule" valign="top"> <p class="First">   Moderate</p> </td><td align="center" class="Botrule Lrule Rrule Toprule" valign="top"> <p class="First">7.3</p> </td><td align="center" class="Botrule Lrule Rrule Toprule" valign="top"> <p class="First">11.6</p> </td> </tr> <tr> <td class="Botrule Lrule Rrule" valign="top"> <p class="First">   Severe</p> </td><td align="center" class="Botrule Lrule Rrule Toprule" valign="top"> <p class="First">0.2</p> </td><td align="center" class="Botrule Lrule Rrule Toprule" valign="top"> <p class="First">0</p> </td> </tr> <tr> <td class="Botrule Lrule Rrule" colspan="3" valign="top"> <p class="First">Muscle pain<a class="Sup" href="#footnote-33">‡</a> </p> </td> </tr> <tr> <td class="Botrule Lrule Rrule" valign="top"> <p class="First">   Any<a class="Sup" href="#footnote-34">§</a> </p> </td><td align="center" class="Botrule Lrule Rrule Toprule" valign="top"> <p class="First">24.4</p> </td><td align="center" class="Botrule Lrule Rrule Toprule" valign="top"> <p class="First">16.0</p> </td> </tr> <tr> <td class="Botrule Lrule Rrule" valign="top"> <p class="First">   Mild</p> </td><td align="center" class="Botrule Lrule Rrule Toprule" valign="top"> <p class="First">15.7</p> </td><td align="center" class="Botrule Lrule Rrule Toprule" valign="top"> <p class="First">9.8</p> </td> </tr> <tr> <td class="Botrule Lrule Rrule" valign="top"> <p class="First">   Moderate</p> </td><td align="center" class="Botrule Lrule Rrule Toprule" valign="top"> <p class="First">8.6</p> </td><td align="center" class="Botrule Lrule Rrule Toprule" valign="top"> <p class="First">6.2</p> </td> </tr> <tr> <td class="Botrule Lrule Rrule" valign="top"> <p class="First">   Severe</p> </td><td align="center" class="Botrule Lrule Rrule Toprule" valign="top"> <p class="First">0</p> </td><td align="center" class="Botrule Lrule Rrule Toprule" valign="top"> <p class="First">0</p> </td> </tr> <tr> <td class="Botrule Lrule Rrule" colspan="3" valign="top"> <p class="First">Joint pain<a class="Sup" href="#footnote-33">‡</a> </p> </td> </tr> <tr> <td class="Botrule Lrule Rrule" valign="top"> <p class="First">   Any<a class="Sup" href="#footnote-34">§</a> </p> </td><td align="center" class="Botrule Lrule Rrule Toprule" valign="top"> <p class="First">12.4</p> </td><td align="center" class="Botrule Lrule Rrule Toprule" valign="top"> <p class="First">10.2</p> </td> </tr> <tr> <td class="Botrule Lrule Rrule" valign="top"> <p class="First">   Mild</p> </td><td align="center" class="Botrule Lrule Rrule Toprule" valign="top"> <p class="First">7.1</p> </td><td align="center" class="Botrule Lrule Rrule Toprule" valign="top"> <p class="First">4.0</p> </td> </tr> <tr> <td class="Botrule Lrule Rrule" valign="top"> <p class="First">   Moderate</p> </td><td align="center" class="Botrule Lrule Rrule Toprule" valign="top"> <p class="First">5.1</p> </td><td align="center" class="Botrule Lrule Rrule Toprule" valign="top"> <p class="First">6.2</p> </td> </tr> <tr> <td class="Botrule Lrule Rrule" valign="top"> <p class="First">   Severe</p> </td><td align="center" class="Botrule Lrule Rrule Toprule" valign="top"> <p class="First">0.2</p> </td><td align="center" class="Botrule Lrule Rrule Toprule" valign="top"> <p class="First">0</p> </td> </tr> <tr> <td class="Botrule Lrule Rrule" colspan="3" valign="top"> <p class="First">Nausea<a class="Sup" href="#footnote-33">‡</a> </p> </td> </tr> <tr> <td class="Botrule Lrule Rrule" valign="top"> <p class="First">   Any<a class="Sup" href="#footnote-34">§</a> </p> </td><td align="center" class="Botrule Lrule Rrule Toprule" valign="top"> <p class="First">11.8</p> </td><td align="center" class="Botrule Lrule Rrule Toprule" valign="top"> <p class="First">10.2</p> </td> </tr> <tr> <td class="Botrule Lrule Rrule" valign="top"> <p class="First">   Mild</p> </td><td align="center" class="Botrule Lrule Rrule Toprule" valign="top"> <p class="First">9.3</p> </td><td align="center" class="Botrule Lrule Rrule Toprule" valign="top"> <p class="First">8.9</p> </td> </tr> <tr> <td class="Botrule Lrule Rrule" valign="top"> <p class="First">   Moderate</p> </td><td align="center" class="Botrule Lrule Rrule Toprule" valign="top"> <p class="First">2.4</p> </td><td align="center" class="Botrule Lrule Rrule Toprule" valign="top"> <p class="First">0.9</p> </td> </tr> <tr> <td class="Botrule Lrule Rrule" valign="top"> <p class="First">   Severe</p> </td><td align="center" class="Botrule Lrule Rrule Toprule" valign="top"> <p class="First">0</p> </td><td align="center" class="Botrule Lrule Rrule Toprule" valign="top"> <p class="First">0.4</p> </td> </tr> <tr> <td class="Botrule Lrule Rrule" colspan="3" valign="top"> <p class="First">Vomiting<a class="Sup" href="#footnote-35" name="footnote-reference-35">¶</a> </p> </td> </tr> <tr> <td class="Botrule Lrule Rrule" valign="top"> <p class="First">   Any<a class="Sup" href="#footnote-34">§</a> </p> </td><td align="center" class="Botrule Lrule Rrule Toprule" valign="top"> <p class="First">2.0</p> </td><td align="center" class="Botrule Lrule Rrule Toprule" valign="top"> <p class="First">1.3</p> </td> </tr> <tr> <td class="Botrule Lrule Rrule" valign="top"> <p class="First">   Mild</p> </td><td align="center" class="Botrule Lrule Rrule Toprule" valign="top"> <p class="First">1.6</p> </td><td align="center" class="Botrule Lrule Rrule Toprule" valign="top"> <p class="First">0.4</p> </td> </tr> <tr> <td class="Botrule Lrule Rrule" valign="top"> <p class="First">   Moderate</p> </td><td align="center" class="Botrule Lrule Rrule Toprule" valign="top"> <p class="First">0.4</p> </td><td align="center" class="Botrule Lrule Rrule Toprule" valign="top"> <p class="First">0.9</p> </td> </tr> <tr> <td class="Botrule Lrule Rrule" valign="top"> <p class="First">   Severe</p> </td><td align="center" class="Botrule Lrule Rrule Toprule" valign="top"> <p class="First">0</p> </td><td align="center" class="Botrule Lrule Rrule Toprule" valign="top"> <p class="First">0</p> </td> </tr> <tr> <td class="Botrule Lrule Rrule" colspan="3" valign="top"> <p class="First">Diarrhea<a class="Sup" href="#footnote-36" name="footnote-reference-36">#</a> </p> </td> </tr> <tr> <td class="Botrule Lrule Rrule" valign="top"> <p class="First">   Any<a class="Sup" href="#footnote-34">§</a> </p> </td><td align="center" class="Botrule Lrule Rrule Toprule" valign="top"> <p class="First">14.9</p> </td><td align="center" class="Botrule Lrule Rrule Toprule" valign="top"> <p class="First">16.9</p> </td> </tr> <tr> <td class="Botrule Lrule Rrule" valign="top"> <p class="First">   Mild</p> </td><td align="center" class="Botrule Lrule Rrule Toprule" valign="top"> <p class="First">11.1</p> </td><td align="center" class="Botrule Lrule Rrule Toprule" valign="top"> <p class="First">12.4</p> </td> </tr> <tr> <td class="Botrule Lrule Rrule" valign="top"> <p class="First">   Moderate</p> </td><td align="center" class="Botrule Lrule Rrule Toprule" valign="top"> <p class="First">3.1</p> </td><td align="center" class="Botrule Lrule Rrule Toprule" valign="top"> <p class="First">3.6</p> </td> </tr> <tr> <td class="Botrule Lrule Rrule Toprule" valign="top"> <p class="First">   Severe</p> </td><td align="center" class="Botrule Lrule Rrule Toprule" valign="top"> <p class="First">0.7</p> </td><td align="center" class="Botrule Lrule Rrule Toprule" valign="top"> <p class="First">0.9</p> </td> </tr> </tbody> </table></div>

Solicited local and systemic reactions had a median duration of 1-2 days.

Unsolicited Adverse Events in Study 4

Unsolicited adverse events occurring within 1 month after vaccination were reported in 7.1% and 7.6% of participants who received ABRYSVO and placebo, respectively. One case of urticaria occurred on the same day as vaccine administration and was considered related to ABRYSVO.

Serious Adverse Events in Study 4

In Study 4, SAEs were reported by 1.1% of participants in the ABRYSVO group and 3.1% in the placebo group. No SAEs were assessed as related to study vaccination.

Concomitant Administration of ABRYSVO with a Seasonal Inactivated Influenza Vaccine

Study 5 (NCT05301322) was a Phase 3, multicenter, parallel group, placebo-controlled, randomized, double-blind study conducted in Australia in adults ≥65 years of age. The study enrolled healthy adults and adults with stable chronic medical conditions not requiring significant change in therapy or hospitalization for worsening disease 6 weeks before enrollment. Participants were enrolled into one of two groups. Participants in the concomitant administration group (n=703) received ABRYSVO and Influenza Vaccine, Adjuvanted (FLUAD QUADRIVALENT) concomitantly and placebo one month later. Participants in the sequential administration group (n=691) received FLUAD QUADRIVALENT and placebo concomitantly and ABRYSVO one month later.

Within 7 days following vaccine administration, fatigue was reported by 30.0% of participants who received ABRYSVO administered concomitantly with FLUAD QUADRIVALENT, 19.1% who received ABRYSVO administered alone, and 27.1% who received FLUAD QUADRIVALENT and placebo concomitantly. There were no other notable differences in reported solicited local and systemic adverse reactions within 7 days following ABRYSVO administered concomitantly with FLUAD QUADRIVALENT compared to ABRYSVO administered alone. Participants were followed for SAEs from administration of the first dose of vaccine through 1 month following the last vaccination. No SAEs were considered related to vaccination.

The following adverse reactions have been identified from spontaneous reports during postmarketing use of ABRYSVO. Because these reactions are reported voluntarily from a population of uncertain size, it is not always possible to reliably estimate their frequency or establish a causal relationship to the vaccine.

Nervous System Disorders: Guillain‑Barré syndrome

Postmarketing Observational Study of the Risk of Guillain‑Barré Syndrome following Vaccination with ABRYSVO

The association between vaccination with ABRYSVO and Guillain‑Barré syndrome (GBS) was evaluated among Medicare beneficiaries 65 years of age and older. Using Medicare claims data, between May 2023 through July 2024, vaccinations with ABRYSVO were identified through Current Procedural Terminology (CPT)/Healthcare Common Procedure Coding System (HCPCS) codes and National Drug Codes, and potential cases of hospitalized GBS among recipients of ABRYSVO were identified through International Classification of Diseases (ICD) codes. GBS diagnoses in claims data were confirmed by medical record review when available.

The risk of GBS following vaccination with ABRYSVO was assessed in self-controlled case series analyses using a risk window of 1 to 42 days post-vaccination and a control window of 43 to 90 days post vaccination. The analyses of all GBS cases based on claims data suggest an increased risk of GBS during the 42 days following vaccination with ABRYSVO, with an incidence rate ratio (GBS cases in the risk window/control window) of 2.02 (95% CI: 0.93, 4.40) and an estimated 9 excess cases of GBS per million doses administered to individuals 65 years of age and older. The background risk of GBS in a study population influences the excess GBS case estimate and may differ between studies, precluding direct comparison to excess GBS case estimates from other vaccine studies or populations.

The analyses of GBS diagnoses in claims data were supported by analyses of GBS cases confirmed by medical record review and by analyses of GBS cases in individuals who received ABRYSVO alone, without other concomitantly administered vaccines. While the results of this observational study suggest an increased risk of GBS with ABRYSVO, available evidence is insufficient to establish a causal relationship.

In Study 6 (NCT04071158) in a concomitant administration study of ABRYSVO and a Tetanus Toxoid, Reduced Diphtheria Toxoid and Acellular Pertussis Vaccine, Adsorbed (Tdap) in non-pregnant women, no safety concerns were identified. Immune responses to RSV A, RSV B, diphtheria, and tetanus were non-inferior to those after separate administration. Lower geometric mean antibody concentrations (GMCs) to the acellular pertussis antigens (pertussis toxin [PT], filamentous hemagglutinin (FHA), and pertactin [PRN]) were measured when ABRYSVO was administered concomitantly with Tdap compared to pertussis GMCs when Tdap was administered alone [see Clinical Studies (14.5)].

{ "type": "p", "children": [], "text": "In Study 6 (NCT04071158) in a concomitant administration study of ABRYSVO and a Tetanus Toxoid, Reduced Diphtheria Toxoid and Acellular Pertussis Vaccine, Adsorbed (Tdap) in non-pregnant women, no safety concerns were identified. Immune responses to RSV A, RSV B, diphtheria, and tetanus were non-inferior to those after separate administration. Lower geometric mean antibody concentrations (GMCs) to the acellular pertussis antigens (pertussis toxin [PT], filamentous hemagglutinin (FHA), and pertactin [PRN]) were measured when ABRYSVO was administered concomitantly with Tdap compared to pertussis GMCs when Tdap was administered alone [see Clinical Studies (14.5)]. " }

Concomitant administration of Tdap with ABRYSVO in pregnant individuals has not been studied.

{ "type": "p", "children": [], "text": "Concomitant administration of Tdap with ABRYSVO in pregnant individuals has not been studied." }

Pregnancy Exposure Registry

There is a pregnancy exposure registry that monitors pregnancy outcomes in individuals exposed to ABRYSVO during pregnancy. Individuals who received ABRYSVO during pregnancy are encouraged to contact, or have their healthcare provider contact, 1-800-616-3791 to enroll in or obtain information about the registry.

Risk Summary

All pregnancies have a risk of birth defect, loss, or other adverse outcomes. In the US general population, the estimated background risk of major birth defects and miscarriages in clinically recognized pregnancies is 2% to 4%, and 15% to 20%, respectively, and the estimated background risk of fetal deaths after 20 weeks is 0.6%.

Study 1 enrolled 7,386 pregnant individuals who were randomized 1:1 and received ABRYSVO or placebo (0.5 mL dose, containing the same buffer ingredients in the same quantities as in a single dose of ABRYSVO [see Description (11)]) revealed no evidence for vaccine-associated increase in the risk of congenital anomalies or fetal deaths. Study 2 evaluated 115 pregnant individuals who received ABRYSVO and 117 who received placebo. A numerical imbalance in preterm births in ABRYSVO recipients was observed compared to placebo recipients in these two clinical studies. Available data are insufficient to establish or exclude a causal relationship between preterm birth and ABRYSVO [see Warnings and Precautions (5.2), Adverse Reactions (6.1), Clinical Considerations (8.1), Data (8.1) and Clinical Studies (14.1)].

A developmental toxicity study was performed in female rabbits administered a vaccine formulation containing two times the antigen content of a single human dose of ABRYSVO prior to and during gestation. The study showed no evidence of harm to the fetus or to postnatal survival, growth, or development (see Animal Data).

Clinical Considerations

Maternal Adverse Reactions

In Study 1, 3,698 pregnant individuals received ABRYSVO and 3,687 received placebo. Local and systemic adverse reactions occurred with greater frequency in the ABRYSVO group. Serious adverse reactions observed in pregnant individuals at a higher rate in the ABRYSVO group compared to the placebo group included pre-eclampsia (1.8% versus 1.4%) and gestational hypertension (1.2% versus 1.1%) [see Adverse Reactions (6.1)].

ABRYSVO has not been studied in pregnant individuals less than 24 weeks gestational age, and those at increased risk for preterm birth.

Fetal/Neonatal Adverse Reactions

The infant safety population included 3,659 and 3,646 infants born to individuals in the ABRYSVO or placebo group, respectively. There were 10 (0.3%) fetal deaths in the ABRYSVO group and 9 (0.2%) in the placebo group. Among the infants born to individuals in the ABRYSVO group and in the placebo group, 207 (5.7%) and 172 (4.7%), respectively, were born preterm [see Warnings and Precautions (5.2), Adverse Reactions (6.1) and Clinical Studies (14.1)]. Low birth weight was observed in 5.1% of participants in the ABRYSVO group versus 4.3% in the placebo group, and neonatal jaundice was observed in 7.3% in the ABRYSVO group versus 6.9% in the placebo group. [see Adverse Reactions (6.1)]. For mortality in the neonatal period among infants born to pregnant individuals in Study 1, there were 3 deaths in the ABRYSVO group and 5 in the placebo group, and for overall mortality including after the neonatal period there were 8 deaths in the ABRYSVO group and 12 in the placebo group. Congenital abnormalities were reported in 5.6% in the ABRYSVO group and 6.7% in the placebo group.

Available data are insufficient to establish or exclude a causal relationship between preterm birth and ABRYSVO. To avoid the potential risk of preterm birth with use of ABRYSVO before 32 weeks of gestation, administer ABRYSVO as indicated in pregnant individuals at 32 through 36 weeks gestational age.

Data

Human Data

In Study 1, 3,698 pregnant individuals received ABRYSVO and 3,687 received placebo at 24 through 36 weeks’ gestation. The infant safety population included 3,659 and 3,646 infants born to individuals in the ABRYSVO or placebo group, respectively. Among the infants born to individuals in the ABRYSVO group and in the placebo group, 207 (5.7%) and 172 (4.7%), respectively, had adverse events of preterm birth and 205 (5.6%) and 245 (6.7%), respectively, had reported congenital malformations or anomalies. There were 10 (0.3%) fetal deaths in the ABRYSVO group and 9 (0.2%) in the placebo group.

Animal Data

A pre- and post-natal developmental toxicity study with an embryo-fetal developmental toxicity phase was performed in female New Zealand White rabbits. Rabbits were administered 4 doses by intramuscular injection: at 3 weeks and at 1 week prior to mating, and on gestation days 10 and 24. On each occasion, rabbits received 0.5 mL of a vaccine formulation containing twice the antigen content of F glycoproteins of RSV A and RSV B (120 mcg RSV preF A and 120 mcg RSV preF B), stabilized in prefusion conformation as contained in a single human dose of ABRYSVO [see Description (11)]. No adverse effects on mating, female fertility, or on embryo/fetal or post-natal survival, growth, or development were observed. There were no vaccine-related fetal malformations or variations.

Risk Summary

It is not known whether ABRYSVO is excreted in human milk. Data are not available to assess the effects of ABRYSVO on the breastfed infant or on milk production/excretion. The developmental and health benefits of breastfeeding should be considered along with the mother’s clinical need for ABRYSVO and any potential adverse effects on the breastfed child from ABRYSVO or from the underlying maternal condition. For preventative vaccines, the underlying maternal condition is susceptibility to disease prevented by the vaccine.

The safety and effectiveness of ABRYSVO to prevent RSV LRTD and severe RSV LRTD in infants born to individuals vaccinated at younger than 10 years of age have not been established.

The safety and effectiveness of ABRYSVO to prevent RSV LRTD in non-pregnant individuals younger than 18 years of age via active immunization have not been established.

ABRYSVO is approved for use in individuals 60 years of age and older. In Study 3, of the 18,574 recipients who received ABRYSVO 63% (n=11,619) were aged 60-69 years of age, 32% (n=5,928) were 70-79 years of age and 5% (n=1,026) were ≥80 years of age [see Adverse Reactions (6.1) and Clinical Studies (14.2)].

ABRYSVO (Respiratory Syncytial Virus Vaccine) is a sterile solution for intramuscular injection. The vaccine is supplied as a vial of Lyophilized Antigen Component that is reconstituted at the time of use with a Sterile Water Diluent Component. The antigen component contains recombinant RSV preF A and RSV preF B.

{ "type": "p", "children": [], "text": "ABRYSVO (Respiratory Syncytial Virus Vaccine) is a sterile solution for intramuscular injection. The vaccine is supplied as a vial of Lyophilized Antigen Component that is reconstituted at the time of use with a Sterile Water Diluent Component. The antigen component contains recombinant RSV preF A and RSV preF B. " }

The RSV preF A and RSV preF B recombinant proteins are expressed in genetically engineered Chinese Hamster Ovary cell lines grown in suspension culture using chemically-defined media, without antibiotics or animal-derived components. The recombinant proteins are purified through a series of column chromatography and filtration steps followed by formulation, filling into vials, and lyophilization.

{ "type": "p", "children": [], "text": "The RSV preF A and RSV preF B recombinant proteins are expressed in genetically engineered Chinese Hamster Ovary cell lines grown in suspension culture using chemically-defined media, without antibiotics or animal-derived components. The recombinant proteins are purified through a series of column chromatography and filtration steps followed by formulation, filling into vials, and lyophilization. " }

After reconstitution, a single dose of ABRYSVO is formulated to contain 120 mcg of RSV stabilized prefusion F proteins (60 mcg RSV preF A and 60 mcg RSV preF B) per 0.5 mL. ABRYSVO also contains the following buffer ingredients: 0.11 mg tromethamine, 1.04 mg tromethamine hydrochloride, 11.3 mg sucrose, 22.5 mg mannitol, 0.08 mg polysorbate 80, and 1.1 mg sodium chloride per 0.5 mL. ABRYSVO is a sterile, clear, and colorless solution.

{ "type": "p", "children": [], "text": "After reconstitution, a single dose of ABRYSVO is formulated to contain 120 mcg of RSV stabilized prefusion F proteins (60 mcg RSV preF A and 60 mcg RSV preF B) per 0.5 mL. ABRYSVO also contains the following buffer ingredients: 0.11 mg tromethamine, 1.04 mg tromethamine hydrochloride, 11.3 mg sucrose, 22.5 mg mannitol, 0.08 mg polysorbate 80, and 1.1 mg sodium chloride per 0.5 mL. ABRYSVO is a sterile, clear, and colorless solution." }

ABRYSVO contains no preservatives. Each dose may also contain residual amounts of host cell proteins (≤0.1% w/w) and DNA (<0.4 ng/mg of total protein) from the manufacturing process.

{ "type": "p", "children": [], "text": "ABRYSVO contains no preservatives. Each dose may also contain residual amounts of host cell proteins (≤0.1% w/w) and DNA (<0.4 ng/mg of total protein) from the manufacturing process. " }

The Act-O-Vial stoppers, vial stoppers and tip cap and rubber plunger of the prefilled syringe are not made with natural rubber latex.

{ "type": "p", "children": [], "text": "The Act-O-Vial stoppers, vial stoppers and tip cap and rubber plunger of the prefilled syringe are not made with natural rubber latex." }

Active Immunization

ABRYSVO induces an immune response against RSVpreF that protects against lower respiratory tract disease caused by RSV.

Passive Immunization

Antibodies to RSV antigens from individuals vaccinated in pregnancy are transferred transplacentally to protect infants younger than 6 months of age against LRTD and severe LRTD caused by RSV.

ABRYSVO has not been evaluated for the potential to cause carcinogenicity, genotoxicity, or impairment of male fertility. A developmental toxicity study in female rabbits revealed no evidence of impaired female fertility after administration of a vaccine formulation containing two times the antigen content of a single human dose of ABRYSVO [see Use in Specific Populations (8.1)].

Study 1 (NCT04424316) was a Phase 3 study that assessed the efficacy of ABRYSVO in the prevention of RSV-associated lower respiratory tract disease (LRTD) in infants born to individuals vaccinated during pregnancy. The study evaluated the efficacy of ABRYSVO to prevent RSV-associated LRTD and severe RSV-LRTD in infants within 90, 120, 150, and 180 days after birth. Participants were randomized (1:1) to receive ABRYSVO (0.5 mL dose) or placebo (0.5 mL dose containing the same buffer ingredients in the same quantities as in a single dose of ABRYSVO [see Description (11)]). This study included sites in both the northern and southern hemispheres. Vaccine efficacy (VE) was defined as the relative risk reduction of the endpoints of severe LRTD caused by RSV and LRTD cause by RSV in infants born to individuals who received ABRYSVO compared to infants born to individuals who received placebo. The demographic characteristics of Study 1 are described in Clinical Trials Experience Section 6.1.

Maternal participants were randomized (1:1) to receive ABRYSVO (3,711) or placebo (3,709). RSV-associated LRTD in infants was defined as a medically attended visit with a reverse transcription-polymerase chain reaction (RT-PCR) confirmed RSV illness with one or more of the following respiratory symptoms: tachypnea (respiratory rate ≥60 breaths/minute [<2 months of age], ≥50 breaths/minute [≥2 to 12 months of age], or ≥40 breaths/minute [≥12-24 months of age]); SpO2 measured in room air <95%; chest wall indrawing. RSV-associated severe LRTD was a subset defined as meeting the LRTD RSV criteria plus at least one of the following: tachypnea (respiratory rate ≥70 breaths per minute [<2 months of age], ≥60 breaths per minute [≥2 to 12 months of age], or ≥50 bpm [≥12 to 24 months of age]); SpO2 measured in room air <93%; high-flow nasal cannula or mechanical ventilation (invasive or noninvasive), ICU admission for >4 hours and/or failure to respond/unconscious. Secondary efficacy endpoints included hospitalizations due to RSV.

The VE results met the statistical criterion for success (a CI lower bound >20%) for reducing severe LRTD due to RSV, at all timepoints to within 180 days. The VE results did not meet the statistical criterion for success (a CI lower bound >20%) for reducing LRTD due to RSV; however, clinically meaningful efficacy was observed after 90 days through 180 days after birth.

Vaccine efficacy information is presented in Tables 8 to 12.

<div class="scrollingtable"><table width="100%"> <caption> <span>Table 8     Vaccine Efficacy of ABRYSVO Against Severe LRTD Caused by RSV – Infants From Birth Through 6 Months of Age by Active Immunization of Pregnant Individuals (Study 1)<a class="Sup" href="#footnote-37" name="footnote-reference-37">*</a></span> </caption> <col width="25%"/> <col width="25%"/> <col width="25%"/> <col width="25%"/> <tfoot> <tr class="First Last"> <td align="left" colspan="4" valign="top">CI – confidence interval; N – number of participants; RSV – respiratory syncytial virus; VE – vaccine efficacy</td> </tr> <tr> <td align="left" colspan="4"> <dl class="Footnote"> <dt> <a href="#footnote-reference-37" name="footnote-37">*</a> </dt> <dd>The prespecified success criterion was met for this endpoint evaluation</dd> <dt> <a href="#footnote-reference-38" name="footnote-38">†</a> </dt> <dd>Evaluable efficacy population</dd> <dt> <a href="#footnote-reference-39" name="footnote-39">‡</a> </dt> <dd>99.5% CI at 90 days; 97.58% CI at later intervals</dd> </dl> </td> </tr> </tfoot> <tbody class="Headless"> <tr class="First"> <td align="center" class="Botrule Lrule Rrule Toprule" valign="top"> <p class="First"> <span class="Bold">Time Period</span> </p> </td><td align="center" class="Botrule Lrule Rrule Toprule" valign="top"> <p class="First"> <span class="Bold">ABRYSVO</span> </p> <p> <span class="Bold">Number of Cases</span> </p> <p> <span class="Bold">N=3,495</span><a class="Sup" href="#footnote-38" name="footnote-reference-38">†</a> </p> </td><td align="center" class="Botrule Lrule Rrule Toprule" valign="top"> <p class="First"> <span class="Bold">PLACEBO</span> </p> <p> <span class="Bold">Number of Cases</span> </p> <p> <span class="Bold">N=3,480</span><a class="Sup" href="#footnote-38">†</a> </p> </td><td align="center" class="Botrule Lrule Rrule Toprule" valign="top"> <p class="First"> <span class="Bold">VE (%)</span> </p> <p> <span class="Bold">(CI)</span><a class="Sup" href="#footnote-39" name="footnote-reference-39">‡</a> </p> </td> </tr> <tr> <td align="center" class="Botrule Lrule Rrule" valign="top"> <p class="First">90 days</p> </td><td align="center" class="Botrule Lrule Rrule Toprule" valign="top"> <p class="First">6</p> </td><td align="center" class="Botrule Lrule Rrule Toprule" valign="top"> <p class="First">33</p> </td><td align="center" class="Botrule Lrule Rrule Toprule" valign="top"> <p class="First">81.8 (40.6, 96.3)</p> </td> </tr> <tr> <td align="center" class="Botrule Lrule Rrule" valign="top"> <p class="First">120 days</p> </td><td align="center" class="Botrule Lrule Rrule Toprule" valign="top"> <p class="First">12</p> </td><td align="center" class="Botrule Lrule Rrule Toprule" valign="top"> <p class="First">46</p> </td><td align="center" class="Botrule Lrule Rrule Toprule" valign="top"> <p class="First">73.9 (45.6, 88.8)</p> </td> </tr> <tr> <td align="center" class="Botrule Lrule Rrule" valign="top"> <p class="First">150 days</p> </td><td align="center" class="Botrule Lrule Rrule Toprule" valign="top"> <p class="First">16</p> </td><td align="center" class="Botrule Lrule Rrule Toprule" valign="top"> <p class="First">55</p> </td><td align="center" class="Botrule Lrule Rrule Toprule" valign="top"> <p class="First">70.9 (44.5, 85.9)</p> </td> </tr> <tr class="Last"> <td align="center" class="Botrule Lrule Rrule Toprule" valign="top"> <p class="First">180 days</p> </td><td align="center" class="Botrule Lrule Rrule Toprule" valign="top"> <p class="First">19</p> </td><td align="center" class="Botrule Lrule Rrule Toprule" valign="top"> <p class="First">62</p> </td><td align="center" class="Botrule Lrule Rrule Toprule" valign="top"> <p class="First">69.4 (44.3, 84.1)</p> </td> </tr> </tbody> </table></div>

<div class="scrollingtable"><table width="100%"> <caption> <span>Table 9     Vaccine Efficacy of ABRYSVO Against LRTD Caused by RSV – Infants From Birth Through 6 Months of Age by Active Immunization of Pregnant Individuals (Study 1)<a class="Sup" href="#footnote-40" name="footnote-reference-40">*</a></span> </caption> <col width="25%"/> <col width="25%"/> <col width="25%"/> <col width="25%"/> <tfoot> <tr class="First Last"> <td align="left" colspan="4" valign="top">CI – confidence interval; N – number of participants; RSV – respiratory syncytial virus; VE – vaccine efficacy</td> </tr> <tr> <td align="left" colspan="4"> <dl class="Footnote"> <dt> <a href="#footnote-reference-40" name="footnote-40">*</a> </dt> <dd>The prespecified success criterion (a CI lower bound &gt;20%) was not met for this endpoint evaluation at 90 days</dd> <dt> <a href="#footnote-reference-41" name="footnote-41">†</a> </dt> <dd>Evaluable efficacy population</dd> <dt> <a href="#footnote-reference-42" name="footnote-42">‡</a> </dt> <dd>99.5% CI at 90 days; 97.58% CI at later intervals</dd> </dl> </td> </tr> </tfoot> <tbody class="Headless"> <tr class="First"> <td align="center" class="Botrule Lrule Rrule Toprule" valign="top"> <p class="First"> <span class="Bold">Time Period</span> </p> </td><td align="center" class="Botrule Lrule Rrule Toprule" valign="top"> <p class="First"> <span class="Bold">ABRYSVO</span> </p> <p> <span class="Bold">Number of Cases</span> </p> <p> <span class="Bold">N=3,495</span><a class="Sup" href="#footnote-41" name="footnote-reference-41">†</a> </p> </td><td align="center" class="Botrule Lrule Rrule Toprule" valign="top"> <p class="First"> <span class="Bold">PLACEBO</span> </p> <p> <span class="Bold">Number of Cases</span> </p> <p> <span class="Bold">N=3,480</span><a class="Sup" href="#footnote-41">†</a> </p> </td><td align="center" class="Botrule Lrule Rrule Toprule" valign="top"> <p class="First"> <span class="Bold">VE (%)</span> </p> <p> <span class="Bold">(CI)</span><a class="Sup" href="#footnote-42" name="footnote-reference-42">‡</a> </p> </td> </tr> <tr> <td align="center" class="Botrule Lrule Rrule" valign="top"> <p class="First">90 days</p> </td><td align="center" class="Botrule Lrule Rrule Toprule" valign="top"> <p class="First">24</p> </td><td align="center" class="Botrule Lrule Rrule Toprule" valign="top"> <p class="First">56</p> </td><td align="center" class="Botrule Lrule Rrule Toprule" valign="top"> <p class="First">57.1 (14.7, 79.8)</p> </td> </tr> <tr> <td align="center" class="Botrule Lrule Rrule" valign="top"> <p class="First">120 days</p> </td><td align="center" class="Botrule Lrule Rrule Toprule" valign="top"> <p class="First">35</p> </td><td align="center" class="Botrule Lrule Rrule Toprule" valign="top"> <p class="First">81</p> </td><td align="center" class="Botrule Lrule Rrule Toprule" valign="top"> <p class="First">56.8 (31.2, 73.5)</p> </td> </tr> <tr> <td align="center" class="Botrule Lrule Rrule" valign="top"> <p class="First">150 days</p> </td><td align="center" class="Botrule Lrule Rrule Toprule" valign="top"> <p class="First">47</p> </td><td align="center" class="Botrule Lrule Rrule Toprule" valign="top"> <p class="First">99</p> </td><td align="center" class="Botrule Lrule Rrule Toprule" valign="top"> <p class="First">52.5 (28.7, 68.9)</p> </td> </tr> <tr class="Last"> <td align="center" class="Botrule Lrule Rrule Toprule" valign="top"> <p class="First">180 days</p> </td><td align="center" class="Botrule Lrule Rrule Toprule" valign="top"> <p class="First">57</p> </td><td align="center" class="Botrule Lrule Rrule Toprule" valign="top"> <p class="First">117</p> </td><td align="center" class="Botrule Lrule Rrule Toprule" valign="top"> <p class="First">51.3 (29.4, 66.8)</p> </td> </tr> </tbody> </table></div>

<div class="scrollingtable"><table width="100%"> <caption> <span>Table 10     Vaccine Efficacy of ABRYSVO Against Severe LRTD Caused by RSV – Infants From Birth Through 6 Months of Age by Active Immunization of Pregnant Individuals at 32 Through 36 Weeks Gestational Age (Study 1)<a class="Sup" href="#footnote-43" name="footnote-reference-43">*</a></span> </caption> <col width="25%"/> <col width="25%"/> <col width="25%"/> <col width="25%"/> <tfoot> <tr class="First Last"> <td align="left" colspan="4" valign="top">CI – confidence interval; N – number of participants; n – number of cases; RSV – respiratory syncytial virus; VE – vaccine efficacy</td> </tr> <tr> <td align="left" colspan="4"> <dl class="Footnote"> <dt> <a href="#footnote-reference-43" name="footnote-43">*</a> </dt> <dd>This descriptive subgroup analysis was not controlled for multiple comparisons; results from 90 days and 180 days are presented.</dd> <dt> <a href="#footnote-reference-44" name="footnote-44">†</a> </dt> <dd>Evaluable efficacy population</dd> <dt> <a href="#footnote-reference-45" name="footnote-45">‡</a> </dt> <dd>95% CI</dd> </dl> </td> </tr> </tfoot> <tbody class="Headless"> <tr class="First"> <td align="center" class="Botrule Lrule Rrule Toprule" valign="top"> <p class="First"> <span class="Bold">Time Period</span> </p> </td><td align="center" class="Botrule Lrule Rrule Toprule" valign="top"> <p class="First"> <span class="Bold">ABRYSVO</span> </p> <p> <span class="Bold">Number of Cases</span> </p> <p> <span class="Bold">N=1,572</span><a class="Sup" href="#footnote-44" name="footnote-reference-44">†</a> </p> </td><td align="center" class="Botrule Lrule Rrule Toprule" valign="top"> <p class="First"> <span class="Bold">PLACEBO</span> </p> <p> <span class="Bold">Number of Cases</span> </p> <p> <span class="Bold">N=1,539</span><a class="Sup" href="#footnote-44">†</a> </p> </td><td align="center" class="Botrule Lrule Rrule Toprule" valign="top"> <p class="First"> <span class="Bold">VE (%)</span> </p> <p> <span class="Bold">(CI)</span><a class="Sup" href="#footnote-45" name="footnote-reference-45">‡</a> </p> </td> </tr> <tr> <td align="center" class="Botrule Lrule Rrule" valign="top"> <p class="First">90 days</p> </td><td align="center" class="Botrule Lrule Rrule Toprule" valign="top"> <p class="First">1</p> </td><td align="center" class="Botrule Lrule Rrule Toprule" valign="top"> <p class="First">11</p> </td><td align="center" class="Botrule Lrule Rrule Toprule" valign="top"> <p class="First">91.1 (38.8, 99.8)</p> </td> </tr> <tr class="Last"> <td align="center" class="Botrule Lrule Rrule Toprule" valign="top"> <p class="First">180 days</p> </td><td align="center" class="Botrule Lrule Rrule Toprule" valign="top"> <p class="First">6</p> </td><td align="center" class="Botrule Lrule Rrule Toprule" valign="top"> <p class="First">25</p> </td><td align="center" class="Botrule Lrule Rrule Toprule" valign="top"> <p class="First">76.5 (41.3, 92.1)</p> </td> </tr> </tbody> </table></div>

<div class="scrollingtable"><table width="100%"> <caption> <span>Table 11     Vaccine Efficacy of ABRYSVO Against LRTD Caused by RSV – Infants From Birth Through 6 Months of Age by Active Immunization of Pregnant Individuals at 32 Through 36 Weeks Gestational Age (Study 1)<a class="Sup" href="#footnote-46" name="footnote-reference-46">*</a></span> </caption> <col width="25%"/> <col width="25%"/> <col width="25%"/> <col width="25%"/> <tfoot> <tr class="First Last"> <td align="left" colspan="4" valign="top">CI – confidence interval; N – number of participants; n – number of cases; RSV – respiratory syncytial virus; VE – vaccine efficacy</td> </tr> <tr> <td align="left" colspan="4"> <dl class="Footnote"> <dt> <a href="#footnote-reference-46" name="footnote-46">*</a> </dt> <dd>This descriptive subgroup analysis was not controlled for multiple comparisons; results from 90 days and 180 days are presented.</dd> <dt> <a href="#footnote-reference-47" name="footnote-47">†</a> </dt> <dd>Evaluable efficacy population</dd> <dt> <a href="#footnote-reference-48" name="footnote-48">‡</a> </dt> <dd>95% CI</dd> </dl> </td> </tr> </tfoot> <tbody class="Headless"> <tr class="First"> <td align="center" class="Botrule Lrule Rrule Toprule" valign="top"> <p class="First"> <span class="Bold">Time Period</span> </p> </td><td align="center" class="Botrule Lrule Rrule Toprule" valign="top"> <p class="First"> <span class="Bold">ABRYSVO</span> </p> <p> <span class="Bold">Number of Cases</span> </p> <p> <span class="Bold">N=1,572</span><a class="Sup" href="#footnote-47" name="footnote-reference-47">†</a> </p> </td><td align="center" class="Botrule Lrule Rrule Toprule" valign="top"> <p class="First"> <span class="Bold">PLACEBO</span> </p> <p> <span class="Bold">Number of Cases</span> </p> <p> <span class="Bold">N=1,539</span><a class="Sup" href="#footnote-47">†</a> </p> </td><td align="center" class="Botrule Lrule Rrule Toprule" valign="top"> <p class="First"> <span class="Bold">VE (%)</span> </p> <p> <span class="Bold">(CI)</span><a class="Sup" href="#footnote-48" name="footnote-reference-48">‡</a> </p> </td> </tr> <tr> <td align="center" class="Botrule Lrule Rrule" valign="top"> <p class="First">90 days</p> </td><td align="center" class="Botrule Lrule Rrule Toprule" valign="top"> <p class="First">14</p> </td><td align="center" class="Botrule Lrule Rrule Toprule" valign="top"> <p class="First">21</p> </td><td align="center" class="Botrule Lrule Rrule Toprule" valign="top"> <p class="First">34.7 (-34.6, 69.3)</p> </td> </tr> <tr class="Last"> <td align="center" class="Botrule Lrule Rrule Toprule" valign="top"> <p class="First">180 days</p> </td><td align="center" class="Botrule Lrule Rrule Toprule" valign="top"> <p class="First">24</p> </td><td align="center" class="Botrule Lrule Rrule Toprule" valign="top"> <p class="First">55</p> </td><td align="center" class="Botrule Lrule Rrule Toprule" valign="top"> <p class="First">57.3 (29.8, 74.7)</p> </td> </tr> </tbody> </table></div>

<div class="scrollingtable"><table width="100%"> <caption> <span>Table 12     Vaccine Efficacy of ABRYSVO Against Hospitalization Due to RSV – Infants From Birth Through 6 Months of Age by Active Immunization of Pregnant Individuals (Study 1)<a class="Sup" href="#footnote-49" name="footnote-reference-49">*</a></span> </caption> <col width="25%"/> <col width="25%"/> <col width="25%"/> <col width="25%"/> <tfoot> <tr class="First Last"> <td align="left" colspan="4" valign="top">CI – confidence interval; N – number of participants; n – number of cases; RSV – respiratory syncytial virus; VE – vaccine efficacy</td> </tr> <tr> <td align="left" colspan="4"> <dl class="Footnote"> <dt> <a href="#footnote-reference-49" name="footnote-49">*</a> </dt> <dd>NCT04424316</dd> <dt> <a href="#footnote-reference-50" name="footnote-50">†</a> </dt> <dd>Evaluable efficacy population</dd> <dt> <a href="#footnote-reference-51" name="footnote-51">‡</a> </dt> <dd>99.17% CI</dd> </dl> </td> </tr> </tfoot> <tbody class="Headless"> <tr class="First"> <td align="center" class="Botrule Lrule Rrule Toprule" valign="top"> <p class="First"> <span class="Bold">Time Period</span> </p> </td><td align="center" class="Botrule Lrule Rrule Toprule" valign="top"> <p class="First"> <span class="Bold">ABRYSVO</span> </p> <p> <span class="Bold">Number of Cases</span> </p> <p> <span class="Bold">N=3,495</span><a class="Sup" href="#footnote-50" name="footnote-reference-50">†</a> </p> </td><td align="center" class="Botrule Lrule Rrule Toprule" valign="top"> <p class="First"> <span class="Bold">PLACEBO</span> </p> <p> <span class="Bold">Number of Cases</span> </p> <p> <span class="Bold">N=3,480</span><a class="Sup" href="#footnote-50">†</a> </p> </td><td align="center" class="Botrule Lrule Rrule Toprule" valign="top"> <p class="First"> <span class="Bold">VE (%)</span> </p> <p> <span class="Bold">(CI)</span><a class="Sup" href="#footnote-51" name="footnote-reference-51">‡</a> </p> </td> </tr> <tr> <td align="center" class="Botrule Lrule Rrule" valign="top"> <p class="First">90 days</p> </td><td align="center" class="Botrule Lrule Rrule Toprule" valign="top"> <p class="First">10</p> </td><td align="center" class="Botrule Lrule Rrule Toprule" valign="top"> <p class="First">31</p> </td><td align="center" class="Botrule Lrule Rrule Toprule" valign="top"> <p class="First">67.7 (15.9, 89.5)</p> </td> </tr> <tr> <td align="center" class="Botrule Lrule Rrule" valign="top"> <p class="First">120 days</p> </td><td align="center" class="Botrule Lrule Rrule Toprule" valign="top"> <p class="First">15</p> </td><td align="center" class="Botrule Lrule Rrule Toprule" valign="top"> <p class="First">37</p> </td><td align="center" class="Botrule Lrule Rrule Toprule" valign="top"> <p class="First">59.5 (8.3, 83.7)</p> </td> </tr> <tr> <td align="center" class="Botrule Lrule Rrule" valign="top"> <p class="First">150 days</p> </td><td align="center" class="Botrule Lrule Rrule Toprule" valign="top"> <p class="First">17</p> </td><td align="center" class="Botrule Lrule Rrule Toprule" valign="top"> <p class="First">39</p> </td><td align="center" class="Botrule Lrule Rrule Toprule" valign="top"> <p class="First">56.4 (5.2, 81.5)</p> </td> </tr> <tr class="Last"> <td align="center" class="Botrule Lrule Rrule Toprule" valign="top"> <p class="First">180 days</p> </td><td align="center" class="Botrule Lrule Rrule Toprule" valign="top"> <p class="First">19</p> </td><td align="center" class="Botrule Lrule Rrule Toprule" valign="top"> <p class="First">44</p> </td><td align="center" class="Botrule Lrule Rrule Toprule" valign="top"> <p class="First">56.8 (10.1, 80.7)</p> </td> </tr> </tbody> </table></div>

Study 3 (NCT05035212) was a Phase 3, multicenter, randomized, double-blind, placebo-controlled study to assess the efficacy and safety of ABRYSVO in the prevention of RSV-associated lower respiratory tract disease in individuals 60 years of age and older. Participants were followed for up to two RSV seasons, approximately 25 months.

Participants were randomized (1:1) to receive ABRYSVO (n=18,487) or placebo (n=18,479). Randomization was stratified by age, 60-69 years (n=23,151, 63%), 70-79 years (n=11,782, 32%), and ≥80 years (n=2,031, 6%). Healthy adults and adults with stable chronic diseases were included. Among enrolled participants 16% had stable chronic cardiopulmonary conditions such as chronic obstructive pulmonary disease (COPD), asthma, or congestive heart failure (CHF).

Starting 14 days after study vaccination (study Day 15), all participants were actively monitored for onset of acute respiratory illness (ARI) symptoms: new or increased sore throat, nasal congestion, nasal discharge, cough, wheezing, sputum production, or shortness of breath. If the participant experienced 1 or more ARI symptoms, a mid-turbinate nasal swab was collected within 7 days of onset of symptoms and tested by reverse transcriptase polymerase chain reaction (RT-PCR) for RSV.

RSV-associated lower respiratory tract disease (RSV-LRTD) was evaluated in Study 3. A case of RSV-LRTD was defined as an RT-PCR confirmed RSV illness with two or more, or three or more, of the following respiratory symptoms within 7 days of symptom onset and lasting more than 1 day during the same illness: new or increased cough, wheezing, sputum production, shortness of breath, or tachypnea (≥25 breaths/min or 15% increase from resting baseline). A case of RSV-associated severe lower respiratory tract disease was defined as a case meeting the RSV-LRTD criteria plus at least one of the following: hospitalization due to RSV-LRTD, new or increased oxygen supplementation, or mechanical ventilation including Continuous Positive Airway Pressure (CPAP).

Vaccine efficacy (VE), against RSV-LRTD, defined as the relative risk reduction of first episode of RSV-LRTD in the ABRYSVO group compared to the placebo group in the first RSV season, was assessed.

The primary analysis of efficacy was conducted when 44 first-episode RSV-LRTD cases with ≥2 symptoms had accrued in the first RSV season. The study met the pre-specified success criteria for demonstration of efficacy of ABRYSVO for the primary objectives of prevention of RSV-LRTD with ≥2 symptoms and prevention of RSV-LRTD with ≥3 symptoms.

Vaccine efficacy information for the primary analysis is presented in Table 13.

<div class="scrollingtable"><table width="100%"> <caption> <span>Table 13     Vaccine Efficacy of ABRYSVO Against RSV-LRTD - Individuals 60 Years of Age and Older – Primary Analysis (Study 3)<a class="Sup" href="#footnote-52" name="footnote-reference-52">*</a></span> </caption> <col width="25%"/> <col width="25%"/> <col width="25%"/> <col width="25%"/> <tfoot> <tr class="First Last"> <td align="left" colspan="4" valign="top">CI – confidence interval; N – number of participants; n = number of cases; RSV – respiratory syncytial virus; VE – vaccine efficacy (VE based on case count ratio is calculated as 1-(P/[1-P]), where P is the number of cases in the ABRYSVO group divided by the total number of cases combined ABRYSVO and placebo)</td> </tr> <tr> <td align="left" colspan="4"> <dl class="Footnote"> <dt> <a href="#footnote-reference-52" name="footnote-52">*</a> </dt> <dd>NCT05035212</dd> <dt> <a href="#footnote-reference-53" name="footnote-53">†</a> </dt> <dd>Evaluable efficacy population</dd> <dt> <a href="#footnote-reference-54" name="footnote-54">‡</a> </dt> <dd>RSV-associated LRTD symptoms included the following: new or increased cough, wheezing, sputum production, shortness of breath, or tachypnea (≥25 breaths/min or 15% increase from resting baseline).</dd> </dl> </td> </tr> </tfoot> <tbody class="Headless"> <tr class="First"> <td align="center" class="Botrule Lrule Rrule Toprule" valign="top"> <p class="First"> <span class="Bold">Efficacy Endpoint</span> </p> <p> <span class="Bold">7 months median follow-up</span> </p> </td><td align="center" class="Botrule Lrule Rrule Toprule" valign="top"> <p class="First"> <span class="Bold">ABRYSVO</span> </p> <p> <span class="Bold">N=16,306</span><a class="Sup" href="#footnote-53" name="footnote-reference-53">†</a> </p> <p> <span class="Bold">n</span> </p> </td><td align="center" class="Botrule Lrule Rrule Toprule" valign="top"> <p class="First"> <span class="Bold">Placebo</span> </p> <p> <span class="Bold">N=16,308</span><a class="Sup" href="#footnote-53">†</a> </p> <p> <span class="Bold">n</span> </p> </td><td align="center" class="Botrule Lrule Rrule Toprule" valign="top"> <p class="First"> <span class="Bold">VE (%)</span> </p> <p> <span class="Bold">(96.66% CI)</span> </p> </td> </tr> <tr> <td class="Botrule Lrule Rrule" valign="top"> <p class="First">First episode of RSV-associated lower respiratory tract disease with ≥2 symptoms<a class="Sup" href="#footnote-54" name="footnote-reference-54">‡</a> </p> </td><td align="center" class="Botrule Lrule Rrule Toprule" valign="top"> <p class="First">11</p> </td><td align="center" class="Botrule Lrule Rrule Toprule" valign="top"> <p class="First">33</p> </td><td align="center" class="Botrule Lrule Rrule Toprule" valign="top"> <p class="First">66.7 (28.8, 85.8)</p> </td> </tr> <tr class="Last"> <td class="Botrule Lrule Rrule Toprule" valign="top"> <p class="First">First episode of RSV-associated lower respiratory tract disease with ≥3 symptoms<a class="Sup" href="#footnote-54">‡</a> </p> </td><td align="center" class="Botrule Lrule Rrule Toprule" valign="top"> <p class="First">2</p> </td><td align="center" class="Botrule Lrule Rrule Toprule" valign="top"> <p class="First">14</p> </td><td align="center" class="Botrule Lrule Rrule Toprule" valign="top"> <p class="First">85.7 (32.0, 98.7)</p> </td> </tr> </tbody> </table></div>

There were 2 cases of RSV-associated severe lower respiratory tract disease in the placebo group and no cases in the ABRYSVO group during the first RSV season. In the second RSV season, 1 case was reported in each group.

Descriptive vaccine efficacy analyses at the end of the first RSV season and combined across the two RSV seasons are presented in Tables 14 and 15.

<div class="scrollingtable"><table class="Noautorules" width="100%"> <caption> <span>Table 14     Descriptive Vaccine Efficacy of ABRYSVO Against RSV LRTD - Individuals 60 Years of Age and Older, End of First RSV Season (Study 3)<a class="Sup" href="#footnote-55" name="footnote-reference-55">*</a></span> </caption> <col width="20%"/> <col width="20%"/> <col width="20%"/> <col width="20%"/> <col width="20%"/> <tfoot> <tr> <td align="left" colspan="5" valign="top">CI – confidence interval; N – number of participants; n = number of cases; RSV – respiratory syncytial virus; VE – vaccine efficacy (VE based on case count ratio is calculated as 1-(P/[1-P]), where P is the number of cases in the ABRYSVO group divided by the total number of cases)</td> </tr> <tr> <td align="left" colspan="5"> <dl class="Footnote"> <dt> <a href="#footnote-reference-55" name="footnote-55">*</a> </dt> <dd>NCT05035212</dd> <dt> <a href="#footnote-reference-56" name="footnote-56">†</a> </dt> <dd>RSV-associated LRTD symptoms included the following: new or increased cough, wheezing, sputum production, shortness of breath, or tachypnea (≥25 breaths/min or 15% increase from resting baseline).</dd> <dt> <a href="#footnote-reference-57" name="footnote-57">‡</a> </dt> <dd>Evaluable efficacy population.</dd> <dt> <a href="#footnote-reference-58" name="footnote-58">§</a> </dt> <dd>VE cannot be reliably estimated due to the small number of accrued cases in the subgroup.</dd> <dt> <a href="#footnote-reference-59" name="footnote-59">¶</a> </dt> <dd>Subgroup of evaluable efficacy population with ≥1 significant underlying condition i.e. heart disease (including congestive heart failure), lung disease (including chronic obstructive pulmonary disease), asthma, diabetes mellitus, liver disease, renal disease, and current tobacco use.</dd> <dt> <a href="#footnote-reference-60" name="footnote-60">#</a> </dt> <dd>Subgroup analyses by age are not presented for RSV-LRTD with ≥3 symptoms due to the limited number of accrued cases in the age subgroups during the first RSV season.</dd> </dl> </td> </tr> </tfoot> <tbody class="Headless"> <tr> <td align="center" class="Botrule Lrule Rrule Toprule" valign="top"> <p class="First"> <span class="Bold">Efficacy Endpoint</span> </p> </td><td align="center" class="Botrule Lrule Rrule Toprule" valign="top"> <p class="First"> <span class="Bold">Analysis Population</span> </p> </td><td align="center" class="Botrule Lrule Rrule Toprule" valign="top"> <p class="First"> <span class="Bold">ABRYSVO</span> </p> <p> <span class="Bold">n/N</span> </p> </td><td align="center" class="Botrule Lrule Rrule Toprule" valign="top"> <p class="First"> <span class="Bold">Placebo</span> </p> <p> <span class="Bold">n/N</span> </p> </td><td align="center" class="Botrule Lrule Rrule Toprule" valign="top"> <p class="First"> <span class="Bold">VE (%)</span> </p> <p> <span class="Bold">(95% CI)</span> </p> </td> </tr> <tr> <td class="Botrule Lrule Rrule" colspan="5" valign="top"> <p class="First"> <span class="Bold">7.4 months median follow-up</span> </p> </td> </tr> <tr> <td class="Botrule Lrule Rrule" rowspan="5" valign="top"> <p class="First">First episode of RSV-associated lower respiratory tract disease with ≥2 symptoms<a class="Sup" href="#footnote-56" name="footnote-reference-56">†</a> </p> </td><td class="Botrule Lrule Rrule Toprule" valign="top"> <p class="First">Overall<a class="Sup" href="#footnote-57" name="footnote-reference-57">‡</a> </p> </td><td align="center" class="Botrule Lrule Rrule Toprule" valign="top"> <p class="First">15/18,050</p> </td><td align="center" class="Botrule Lrule Rrule Toprule" valign="top"> <p class="First">43/18,074</p> </td><td align="center" class="Botrule Lrule Rrule Toprule" valign="top"> <p class="First">65.1 (35.9, 82.0)</p> </td> </tr> <tr> <td class="Botrule Lrule Rrule Toprule" valign="top"> <p class="First">Age 60-69 years</p> </td><td align="center" class="Botrule Lrule Rrule Toprule" valign="top"> <p class="First">10/11,305</p> </td><td align="center" class="Botrule Lrule Rrule Toprule" valign="top"> <p class="First">25/11,351</p> </td><td align="center" class="Botrule Lrule Rrule Toprule" valign="top"> <p class="First">60.0 (13.8, 82.9)</p> </td> </tr> <tr> <td class="Botrule Lrule Rrule Toprule" valign="top"> <p class="First">Age 70-79 years</p> </td><td align="center" class="Botrule Lrule Rrule Toprule" valign="top"> <p class="First">4/5,750</p> </td><td align="center" class="Botrule Lrule Rrule Toprule" valign="top"> <p class="First">12/5,742</p> </td><td align="center" class="Botrule Lrule Rrule Toprule" valign="top"> <p class="First">66.7 (-10.0, 92.2)<a class="Sup" href="#footnote-58" name="footnote-reference-58">§</a> </p> </td> </tr> <tr> <td class="Botrule Lrule Rrule Toprule" valign="top"> <p class="First">Age ≥ 80 years</p> </td><td align="center" class="Botrule Lrule Rrule Toprule" valign="top"> <p class="First">1/995</p> </td><td align="center" class="Botrule Lrule Rrule Toprule" valign="top"> <p class="First">6/981</p> </td><td align="center" class="Botrule Lrule Rrule Toprule" valign="top"> <p class="First">83.3 (-37.4, 99.6)<a class="Sup" href="#footnote-58">§</a> </p> </td> </tr> <tr> <td class="Botrule Lrule Rrule Toprule" valign="top"> <p class="First">With ≥1 significant underlying condition<a class="Sup" href="#footnote-59" name="footnote-reference-59">¶</a> </p> </td><td align="center" class="Botrule Lrule Rrule Toprule" valign="top"> <p class="First">8/9,387</p> </td><td align="center" class="Botrule Lrule Rrule Toprule" valign="top"> <p class="First">22/9,448</p> </td><td align="center" class="Botrule Lrule Rrule Toprule" valign="top"> <p class="First">63.6 (15.2, 86.0)</p> </td> </tr> <tr> <td class="Botrule Lrule Rrule" rowspan="2" valign="top"> <p class="First">First episode of RSV associated lower respiratory tract disease with ≥3 symptoms<a class="Sup" href="#footnote-56">†</a> </p> </td><td class="Botrule Lrule Rrule Toprule" valign="top"> <p class="First">Overall<a class="Sup" href="#footnote-57">‡</a><a class="Sup" href="#footnote-60" name="footnote-reference-60">#</a> </p> </td><td align="center" class="Botrule Lrule Rrule Toprule" valign="top"> <p class="First">2/18,050</p> </td><td align="center" class="Botrule Lrule Rrule Toprule" valign="top"> <p class="First">18/18,074</p> </td><td align="center" class="Botrule Lrule Rrule Toprule" valign="top"> <p class="First">88.9 (53.6, 98.7)</p> </td> </tr> <tr> <td class="Botrule Lrule Rrule Toprule" valign="top"> <p class="First">With ≥1 significant underlying condition<a class="Sup" href="#footnote-59">¶</a> </p> </td><td align="center" class="Botrule Lrule Rrule Toprule" valign="top"> <p class="First">2/9,387</p> </td><td align="center" class="Botrule Lrule Rrule Toprule" valign="top"> <p class="First">11/9,448</p> </td><td align="center" class="Botrule Lrule Rrule Toprule" valign="top"> <p class="First">81.8 (16.7, 98.0)</p> </td> </tr> </tbody> </table></div>

For RSV-A associated LRTD at the end of the first season, descriptive VE was 81.3% (95% CI 34.5, 96.5) for cases with ≥2 LRTD symptoms and 80.0% (95% CI -78.7, 99.6) for cases with ≥3 LRTD symptoms. For RSV-B associated LRTD at the end of the first season, descriptive VE was 53.8% (95% CI 5.2, 78.8) for cases with ≥2 LRTD symptoms and 91.7% (95% CI 43.7, 99.8) for cases with ≥3 LRTD symptoms.

In the second RSV season, VE against RSV associated LRTD with ≥2 symptoms was 55.7% (95% CI 34.7, 70.4; 39 cases in the ABRYSVO group and 88 cases in the placebo group) and with ≥3 symptoms was 77.8% (95% CI 51.4, 91.1; 8 cases in the ABRYSVO group and 36 cases in the placebo group). The median duration of follow up was 7.7 months in the second season.

<div class="scrollingtable"><table width="100%"> <caption> <span>Table 15     Descriptive Vaccine Efficacy of ABRYSVO Against RSV LRTD - Individuals 60 Years of Age and Older, Across Two RSV Seasons (Study 3)<a class="Sup" href="#footnote-61" name="footnote-reference-61">*</a></span> </caption> <col width="20%"/> <col width="20%"/> <col width="20%"/> <col width="20%"/> <col width="20%"/> <tfoot> <tr class="First Last"> <td align="left" colspan="5" valign="top">CI – confidence interval; N – number of participants; n = number of cases; RSV – respiratory syncytial virus; VE – vaccine efficacy (VE based on case count ratio is calculated as 1-(P/[1-P]), where P is the number of cases in the ABRYSVO group divided by the total number of cases)</td> </tr> <tr> <td align="left" colspan="5"> <dl class="Footnote"> <dt> <a href="#footnote-reference-61" name="footnote-61">*</a> </dt> <dd>NCT05035212</dd> <dt> <a href="#footnote-reference-62" name="footnote-62">†</a> </dt> <dd>RSV-associated LRTD symptoms included the following: new or increased cough, wheezing, sputum production, shortness of breath, or tachypnea (≥25 breaths/min or 15% increase from resting baseline).</dd> <dt> <a href="#footnote-reference-63" name="footnote-63">‡</a> </dt> <dd>Evaluable efficacy population.</dd> <dt> <a href="#footnote-reference-64" name="footnote-64">§</a> </dt> <dd>VE cannot be reliably estimated due to the small number of accrued cases in the subgroup.</dd> <dt> <a href="#footnote-reference-65" name="footnote-65">¶</a> </dt> <dd>Subgroup of evaluable efficacy population with ≥1 significant underlying condition i.e. heart disease (including congestive heart failure), lung disease (including chronic obstructive pulmonary disease), asthma, diabetes mellitus, liver disease, renal disease, and current tobacco use.</dd> </dl> </td> </tr> </tfoot> <tbody class="Headless"> <tr class="First Toprule"> <td align="center" class="Botrule Lrule Rrule Toprule" valign="top"> <p class="First"> <span class="Bold">Efficacy Endpoint</span> </p> </td><td align="center" class="Botrule Lrule Rrule Toprule" valign="top"> <p class="First"> <span class="Bold">Analysis Population</span> </p> </td><td align="center" class="Botrule Lrule Rrule Toprule" valign="top"> <p class="First"> <span class="Bold">ABRYSVO</span> </p> <p> <span class="Bold">n/N</span> </p> </td><td align="center" class="Botrule Lrule Rrule Toprule" valign="top"> <p class="First"> <span class="Bold">Placebo</span> </p> <p> <span class="Bold">n/N</span> </p> </td><td align="center" class="Botrule Lrule Rrule Toprule" valign="top"> <p class="First"> <span class="Bold">VE (%)</span> </p> <p> <span class="Bold">(95% CI)</span> </p> </td> </tr> <tr> <td class="Botrule Lrule Rrule Toprule" colspan="5" valign="top"> <p class="First"> <span class="Bold">16.9 months median time since vaccination</span> </p> </td> </tr> <tr> <td class="Botrule Lrule Rrule" rowspan="5" valign="top"> <p class="First">First episode of RSV-associated lower respiratory tract disease with ≥2 symptoms<a class="Sup" href="#footnote-62" name="footnote-reference-62">†</a> </p> </td><td class="Botrule Lrule Rrule Toprule" valign="top"> <p class="First">Overall<a class="Sup" href="#footnote-63" name="footnote-reference-63">‡</a> </p> </td><td align="center" class="Botrule Lrule Rrule Toprule" valign="top"> <p class="First">15/18,050</p> </td><td align="center" class="Botrule Lrule Rrule Toprule" valign="top"> <p class="First">131/18,074</p> </td><td align="center" class="Botrule Lrule Rrule Toprule" valign="top"> <p class="First">58.8 (43.0, 70.6)</p> </td> </tr> <tr> <td class="Botrule Lrule Rrule Toprule" valign="top"> <p class="First">Age 60-69 years</p> </td><td align="center" class="Botrule Lrule Rrule Toprule" valign="top"> <p class="First">34/11,305</p> </td><td align="center" class="Botrule Lrule Rrule Toprule" valign="top"> <p class="First">80/11,351</p> </td><td align="center" class="Botrule Lrule Rrule Toprule" valign="top"> <p class="First">57.5 (35.8, 72.4)</p> </td> </tr> <tr> <td class="Botrule Lrule Rrule Toprule" valign="top"> <p class="First">Age 70-79 years</p> </td><td align="center" class="Botrule Lrule Rrule Toprule" valign="top"> <p class="First">15/5,750</p> </td><td align="center" class="Botrule Lrule Rrule Toprule" valign="top"> <p class="First">40/5,742</p> </td><td align="center" class="Botrule Lrule Rrule Toprule" valign="top"> <p class="First">62.5 (30.6, 80.8)</p> </td> </tr> <tr> <td class="Botrule Lrule Rrule Toprule" valign="top"> <p class="First">Age ≥ 80 years</p> </td><td align="center" class="Botrule Lrule Rrule Toprule" valign="top"> <p class="First">5/995</p> </td><td align="center" class="Botrule Lrule Rrule Toprule" valign="top"> <p class="First">11/981</p> </td><td align="center" class="Botrule Lrule Rrule Toprule" valign="top"> <p class="First">54.5 (-41.9, 87.6)<a class="Sup" href="#footnote-64" name="footnote-reference-64">§</a> </p> </td> </tr> <tr> <td class="Botrule Lrule Rrule Toprule" valign="top"> <p class="First">With ≥1 significant underlying condition<a class="Sup" href="#footnote-65" name="footnote-reference-65">¶</a> </p> </td><td align="center" class="Botrule Lrule Rrule Toprule" valign="top"> <p class="First">36/9,387</p> </td><td align="center" class="Botrule Lrule Rrule Toprule" valign="top"> <p class="First">71/9,448</p> </td><td align="center" class="Botrule Lrule Rrule Toprule" valign="top"> <p class="First">49.3 (23.2, 67.0)</p> </td> </tr> <tr> <td class="Botrule Lrule Rrule" rowspan="5" valign="top"> <p class="First">First episode of RSV-associated lower respiratory tract disease with ≥3 symptoms<a class="Sup" href="#footnote-62">†</a> </p> </td><td class="Botrule Lrule Rrule Toprule" valign="top"> <p class="First">Overall<a class="Sup" href="#footnote-63">‡</a> </p> </td><td align="center" class="Botrule Lrule Rrule Toprule" valign="top"> <p class="First">10/18,050</p> </td><td align="center" class="Botrule Lrule Rrule Toprule" valign="top"> <p class="First">54/18,074</p> </td><td align="center" class="Botrule Lrule Rrule Toprule" valign="top"> <p class="First">81.5 (63.3, 91.6)</p> </td> </tr> <tr> <td class="Botrule Lrule Rrule Toprule" valign="top"> <p class="First">Age 60-69 years</p> </td><td align="center" class="Botrule Lrule Rrule Toprule" valign="top"> <p class="First">7/11,305</p> </td><td align="center" class="Botrule Lrule Rrule Toprule" valign="top"> <p class="First">38/11,351</p> </td><td align="center" class="Botrule Lrule Rrule Toprule" valign="top"> <p class="First">81.6 (58.2, 93.1)</p> </td> </tr> <tr> <td class="Botrule Lrule Rrule Toprule" valign="top"> <p class="First">Age 70-79 years</p> </td><td align="center" class="Botrule Lrule Rrule Toprule" valign="top"> <p class="First">3/5,750</p> </td><td align="center" class="Botrule Lrule Rrule Toprule" valign="top"> <p class="First">11/5,742</p> </td><td align="center" class="Botrule Lrule Rrule Toprule" valign="top"> <p class="First">72.7 (-3.2, 95.1)<a class="Sup" href="#footnote-64">§</a> </p> </td> </tr> <tr> <td class="Botrule Lrule Rrule Toprule" valign="top"> <p class="First">Age ≥ 80 years</p> </td><td align="center" class="Botrule Lrule Rrule Toprule" valign="top"> <p class="First">0/995</p> </td><td align="center" class="Botrule Lrule Rrule Toprule" valign="top"> <p class="First">5/981</p> </td><td align="center" class="Botrule Lrule Rrule Toprule" valign="top"> <p class="First">100.0 (-9.1, 100.0)<a class="Sup" href="#footnote-64">§</a> </p> </td> </tr> <tr class="Botrule Last"> <td class="Botrule Lrule Rrule Toprule" valign="top"> <p class="First">With ≥1 significant underlying condition<a class="Sup" href="#footnote-65">¶</a> </p> </td><td align="center" class="Botrule Lrule Rrule Toprule" valign="top"> <p class="First">9/9,387</p> </td><td align="center" class="Botrule Lrule Rrule Toprule" valign="top"> <p class="First">34/9,448</p> </td><td align="center" class="Botrule Lrule Rrule Toprule" valign="top"> <p class="First">73.5 (43.6, 88.8)</p> </td> </tr> </tbody> </table></div>

For RSV-A associated LRTD across two RSV seasons, descriptive VE was 66.3% (95% CI 47.2, 79.0) for cases with ≥2 LRTD symptoms and 80.6% (95% CI 52.9, 93.4) for cases with ≥3 LRTD symptoms. For RSV-B associated LRTD across two RSV seasons, descriptive VE was 50.0% (95% CI 18.5, 70.0) for cases with ≥2 LRTD symptoms and 86.4% (95% CI 54.6, 97.4) for cases with ≥3 LRTD symptoms.

Study 4 was a Phase 3, multicenter, randomized, double‑blind, placebo‑controlled study to assess the safety and immunogenicity of ABRYSVO in individuals 18 through 59 years of age considered to be at increased risk of LRTD caused by RSV due to chronic medical conditions. Study 4 enrolled individuals who had chronic pulmonary (including asthma), cardiovascular (excluding isolated hypertension), renal, hepatic, neurologic, hematologic or metabolic disorders (including diabetes mellitus and hyper/hypothyroidism) [see Adverse Reactions (6.1)]. Effectiveness was assessed by comparison of the RSV neutralizing geometric mean titers (GMTs) and seroresponse rates of the evaluable immunogenicity population in Study 4 who received ABRYSVO (n=437) to those of a subgroup of individuals from select sites in the United States and Japan in Study 3 (n=410) (Tables 16 and 17). Participants in the Study 3 subgroup were 60 years of age or older; 44% had chronic medical conditions.

Non-inferiority was demonstrated for the ratio of neutralizing GMTs for RSV A and RSV B (Study 4/Study 3 subgroup; lower bounds of the 2‑sided 95% CIs >0.667) (Table 16), and the percentage difference in neutralizing titer seroresponse rates for RSV A and RSV B (Study 4 minus Study 3; lower bounds of the 2‑sided 95% CIs >-10%) (Table 17).

<div class="scrollingtable"><table class="Noautorules" width="100%"> <caption> <span>Table 16     Comparison of Model Adjusted RSV Neutralizing GMTs at 1 Month After Vaccination with ABRYSVO, 18 Through 59 Years at Increased Risk of LRTD caused by RSV (Study 4)<a class="Sup" href="#footnote-66" name="footnote-reference-66">*</a> versus 60 Years and Older (Study 3)<a class="Sup" href="#footnote-67" name="footnote-reference-67">†</a></span> </caption> <col width="25%"/> <col width="25%"/> <col width="25%"/> <col width="25%"/> <tfoot> <tr> <td align="left" colspan="4" valign="top">CI – confidence interval; GMR – geometric mean ratio; GMT – geometric mean titer</td> </tr> <tr> <td align="left" colspan="4"> <dl class="Footnote"> <dt> <a href="#footnote-reference-66" name="footnote-66">*</a> </dt> <dd>NCT05842967</dd> <dt> <a href="#footnote-reference-67" name="footnote-67">†</a> </dt> <dd>NCT05035212</dd> <dt> <a href="#footnote-reference-68" name="footnote-68">‡</a> </dt> <dd>Analysis of covariance adjusted with baseline titer and sex.</dd> <dt> <a href="#footnote-reference-69" name="footnote-69">§</a> </dt> <dd>Non-inferiority was met if the lower bound of the 2-sided CI of adjusted GMR (Study 4/Study3) &gt;0.667 (1.5-fold NI criterion) for both RSV A and RSV B.</dd> </dl> </td> </tr> </tfoot> <tbody class="Headless"> <tr> <td align="center" class="Botrule Lrule Rrule Toprule" valign="top"> <p class="First"> <span class="Bold">RSV subgroups</span> </p> </td><td align="center" class="Botrule Lrule Rrule Toprule" valign="top"> <p class="First"> <span class="Bold">Study 4</span><a class="Sup" href="#footnote-66">*</a> </p> <p> <span class="Bold">18-59 years of age at high risk</span> </p> <p> <span class="Bold">N=435-437</span> </p> <p> <span class="Bold">Adjusted GMT</span><a class="Sup" href="#footnote-68" name="footnote-reference-68">‡</a> </p> <p> <span class="Bold">(95% CI)</span> </p> </td><td align="center" class="Botrule Lrule Rrule Toprule" valign="top"> <p class="First"> <span class="Bold">Study 3</span><a class="Sup" href="#footnote-67">†</a> </p> <p> <span class="Bold">≥60 years</span> </p> <p> <span class="Bold">N=408</span> </p> <p> <span class="Bold">Adjusted GMT</span><a class="Sup" href="#footnote-68">‡</a> </p> <p> <span class="Bold">(95% CI)</span> </p> </td><td align="center" class="Botrule Lrule Rrule Toprule" valign="top"> <p class="First"> <span class="Bold">Adjusted GMR</span><a class="Sup" href="#footnote-68">‡</a><span class="Bold"><span class="Sup">,</span></span><a class="Sup" href="#footnote-69" name="footnote-reference-69">§</a> </p> <p> <span class="Bold">(95% CI)</span> </p> </td> </tr> <tr> <td align="center" class="Botrule Lrule Rrule" valign="top"> <p class="First"> <span class="Bold">A</span> </p> </td><td align="center" class="Botrule Lrule Rrule Toprule" valign="top"> <p class="First">41097 (37986, 44463)</p> </td><td align="center" class="Botrule Lrule Rrule Toprule" valign="top"> <p class="First">26225 (24143, 28486)</p> </td><td align="center" class="Botrule Lrule Rrule Toprule" valign="top"> <p class="First">1.57 (1.396, 1.759)</p> </td> </tr> <tr> <td align="center" class="Botrule Lrule Rrule Toprule" valign="top"> <p class="First"> <span class="Bold">B</span> </p> </td><td align="center" class="Botrule Lrule Rrule Toprule" valign="top"> <p class="First">37416 (34278, 40842)</p> </td><td align="center" class="Botrule Lrule Rrule Toprule" valign="top"> <p class="First">24680 (22504, 27065)</p> </td><td align="center" class="Botrule Lrule Rrule Toprule" valign="top"> <p class="First">1.52 (1.333, 1.725)</p> </td> </tr> </tbody> </table></div>

<div class="scrollingtable"><table class="Noautorules" width="100%"> <caption> <span>Table 17     Comparison of RSV Neutralizing Titer Seroresponse<a class="Sup" href="#footnote-70" name="footnote-reference-70">*</a> Rates 1 Month After Vaccination with ABRYSVO, 18 Through 59 Years at Increased Risk of LRTD caused by RSV (Study 4)<a class="Sup" href="#footnote-71" name="footnote-reference-71">†</a> versus 60 Years and Older (Study 3)<a class="Sup" href="#footnote-72" name="footnote-reference-72">‡</a></span> </caption> <col width="25%"/> <col width="25%"/> <col width="25%"/> <col width="25%"/> <tfoot> <tr> <td align="left" colspan="4" valign="top">CI - confidence interval</td> </tr> <tr> <td align="left" colspan="4"> <dl class="Footnote"> <dt> <a href="#footnote-reference-70" name="footnote-70">*</a> </dt> <dd>Seroresponse is defined as achieving a ≥4-fold rise from baseline if the baseline measurement is above the lower limit of quantitation (LLOQ). If the baseline measurement is below the LLOQ, a post-vaccination assay result ≥4 × LLOQ is considered a seroresponse.</dd> <dt> <a href="#footnote-reference-71" name="footnote-71">†</a> </dt> <dd>NCT05842967</dd> <dt> <a href="#footnote-reference-72" name="footnote-72">‡</a> </dt> <dd>NCT05035212</dd> <dt> <a href="#footnote-reference-73" name="footnote-73">§</a> </dt> <dd>Non-inferiority was met if the lower bound of the 2-sided CI for the percentage difference (Study 4 minus Study 3) &gt;-10% (10% NI criterion) for both RSV A and RSV B.</dd> </dl> </td> </tr> </tfoot> <tbody class="Headless"> <tr> <td align="center" class="Botrule Lrule Rrule Toprule" valign="top"> <p class="First"> <span class="Bold">RSV subgroups</span> </p> </td><td align="center" class="Botrule Lrule Rrule Toprule" valign="top"> <p class="First"> <span class="Bold">Study 4</span> </p> <p> <span class="Bold">18-59 years of age at high risk</span> </p> <p> <span class="Bold">N=435-437</span> </p> <p> <span class="Bold">% (95% CI)</span> </p> </td><td align="center" class="Botrule Lrule Rrule Toprule" valign="top"> <p class="First"> <span class="Bold">Study 3</span> </p> <p> <span class="Bold">≥60 years</span> </p> <p> <span class="Bold">N=408</span> </p> <p> <span class="Bold">% (95% CI)</span> </p> </td><td align="center" class="Botrule Lrule Rrule Toprule" valign="top"> <p class="First"> <span class="Bold">Percentage Difference</span><a class="Sup" href="#footnote-73" name="footnote-reference-73">§</a><span class="Bold"> (95% CI)</span> </p> </td> </tr> <tr> <td align="center" class="Botrule Lrule Rrule" valign="top"> <p class="First"> <span class="Bold">A</span> </p> </td><td align="center" class="Botrule Lrule Rrule Toprule" valign="top"> <p class="First">93 (90.3, 95.3)</p> </td><td align="center" class="Botrule Lrule Rrule Toprule" valign="top"> <p class="First">88 (84.4, 91.0)</p> </td><td align="center" class="Botrule Lrule Rrule Toprule" valign="top"> <p class="First">5.1 (1.2, 9.2)</p> </td> </tr> <tr> <td align="center" class="Botrule Lrule Rrule Toprule" valign="top"> <p class="First"> <span class="Bold">B</span> </p> </td><td align="center" class="Botrule Lrule Rrule Toprule" valign="top"> <p class="First">93 (90.6, 95.5)</p> </td><td align="center" class="Botrule Lrule Rrule Toprule" valign="top"> <p class="First">85 (81.2, 88.4)</p> </td><td align="center" class="Botrule Lrule Rrule Toprule" valign="top"> <p class="First">8.3 (4.2, 12.6)</p> </td> </tr> </tbody> </table></div>

In Study 5 (NCT05301322) [See Adverse Reactions (6.1)], antibody responses to antigens contained in ABRYSVO and FLUAD QUADRIVALENT were assessed 1 month after vaccination in individuals 65 years of age and older.

Immunologic non-inferiority was demonstrated for concomitant administration of ABRYSVO and FLUAD QUADRIVALENT as compared to sequential administration. The lower limits of the 2-sided 95% CIs for the Geometric Mean Titer Ratio (GMR) (concomitant administration group versus sequential administration group) for RSV A and RSV B neutralizing titers (NT) and hemagglutination inhibition (HAI) titers against influenza strains A/Victoria, A/Darwin, B/Austria, and B/Phuket were above 0.667 (the predefined 1.5-fold non-inferiority criterion).

Study 6 was a Phase 2, placebo-controlled, randomized, observer-blind study to evaluate the safety, tolerability, and immunogenicity of ABRYSVO (at dose levels 120 µg and 240 µg, with or without Al(OH)3) when administered concomitantly with Tdap in non-pregnant women 18 through 49 years of age.

Antibody responses to antigens contained in ABRYSVO and Tdap were assessed 1 month after vaccination in a population of non-pregnant adult individuals. Lower geometric mean antibody concentrations (GMCs) to the acellular pertussis antigens (pertussis toxin [PT], filamentous hemagglutinin (FHA), and pertactin [PRN]) were observed when ABRYSVO was administered concomitantly with a tetanus, diphtheria and acellular pertussis vaccine (Tdap) compared to pertussis GMCs when Tdap was administered alone. The lower limit (LL) of the 2-sided 95% confidence interval of the GMC ratio (GMC ABRYSVO+Tdap /GMC Tdap) was 0.64 for PT, 0.50 for FHA, and 0.48 for PRN, which did not meet the pre-specified non-inferiority criterion (lower limit of the 95% confidence interval for the GMC ratio is >0.67). The clinical relevance of this finding is unknown. The non-inferiority criteria for tetanus, diphtheria and RSV vaccine antigens were met [see Drug Interactions (7)].

ABRYSVO Act-O-Vial presentation is supplied in cartons of 1 and 10 Act-O-Vials, without syringes or needles. Each Act-O-Vial contains both the Lyophilized Antigen and Sterile Water Diluent (NDC 0069-2465-19).

<div class="scrollingtable"><table width="50%"> <col width="24%"/> <col width="33%"/> <tbody class="Headless"> <tr class="First Toprule"> <td class="Botrule Lrule Rrule Toprule" valign="top"> <p class="First">Carton: 1 Act-O-Vial</p> </td><td class="Botrule Lrule Rrule Toprule" valign="top"> <p class="First">NDC 0069-2465-01</p> </td> </tr> <tr class="Botrule Last"> <td class="Botrule Lrule Rrule Toprule" valign="top"> <p class="First">Carton: 10 Act-O-Vials</p> </td><td class="Botrule Lrule Rrule Toprule" valign="top"> <p class="First">NDC 0069-2465-10</p> </td> </tr> </tbody> </table></div>

ABRYSVO vial and prefilled syringe presentation is supplied in cartons of 1, 5, and 10 kits, without needles. Each kit includes a vial of Lyophilized Antigen Component (NDC 0069-0207-01), a prefilled syringe containing Sterile Water Diluent Component (NDC 0069-0250-01), and a vial adapter.

<div class="scrollingtable"><table width="50%"> <col width="24%"/> <col width="33%"/> <tbody class="Headless"> <tr class="First Toprule"> <td class="Botrule Lrule Rrule Toprule" valign="top"> <p class="First">Carton: 1 kit</p> </td><td class="Botrule Lrule Rrule Toprule" valign="top"> <p class="First">NDC 0069-0344-01</p> </td> </tr> <tr> <td class="Botrule Lrule Rrule" valign="top"> <p class="First">Carton: 5 kits</p> </td><td class="Botrule Lrule Rrule Toprule" valign="top"> <p class="First">NDC 0069-0344-05</p> </td> </tr> <tr class="Botrule Last"> <td class="Botrule Lrule Rrule Toprule" valign="top"> <p class="First">Carton: 10 kits</p> </td><td class="Botrule Lrule Rrule Toprule" valign="top"> <p class="First">NDC 0069-0344-10</p> </td> </tr> </tbody> </table></div>

ABRYSVO vial and vial presentation is supplied in cartons of 5 and 10 doses packaged without syringes or needles. Each carton includes vials of Lyophilized Antigen Component (NDC 0069-0207-01) and vials of Sterile Water Diluent Component (NDC 0069-0651-01).

<div class="scrollingtable"><table width="50%"> <col width="24%"/> <col width="33%"/> <tbody class="Headless"> <tr class="First Toprule"> <td class="Botrule Lrule Rrule Toprule" valign="top"> <p class="First">Carton: 5 doses</p> </td><td class="Botrule Lrule Rrule Toprule" valign="top"> <p class="First">NDC 0069-1265-10</p> </td> </tr> <tr class="Botrule Last"> <td class="Botrule Lrule Rrule Toprule" valign="top"> <p class="First">Carton: 10 doses</p> </td><td class="Botrule Lrule Rrule Toprule" valign="top"> <p class="First">NDC 0069-1265-20</p> </td> </tr> </tbody> </table></div>

The Act-O-Vial stoppers, vial stoppers and the tip cap and rubber plunger of the prefilled syringe are not made with natural rubber latex.

Storage Before Reconstitution

Store refrigerated at 2°C to 8°C (36°F to 46°F) in the original carton. Do not freeze. Discard if the carton has been frozen.

Storage After Reconstitution

After reconstitution, administer ABRYSVO immediately or store at room temperature [15ºC to 30ºC (59ºF to 86ºF)] and use within 4 hours. Do not freeze reconstituted vaccine.

Prior to administration of this vaccine:

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This product's labeling may have been updated. For the most recent prescribing information, please visit www.pfizer.com.

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Manufactured byPfizer Inc.NY, NY 10001US License No. 2001

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LAB-1498-8.0

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NDC 0069-0344-10Rx only

{ "type": "p", "children": [], "text": "NDC 0069-0344-10Rx only" }

NOTICE: Lyophilized Antigen Component and SterileWater Diluent Component must be combined before use.

{ "type": "p", "children": [], "text": "NOTICE: Lyophilized Antigen Component and SterileWater Diluent Component must be combined before use." }

Respiratory SyncytialVirus VaccineABRYSVO®

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For Individuals 60 Years and Older

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For Individuals 18 through 59 Years at Increased Riskfor Lower Respiratory Tract Disease caused by RSV

{ "type": "p", "children": [], "text": "For Individuals 18 through 59 Years at Increased Riskfor Lower Respiratory Tract Disease caused by RSV" }

For Pregnant Individuals at 32 through 36 Weeks Gestation

{ "type": "p", "children": [], "text": "For Pregnant Individuals at 32 through 36 Weeks Gestation" }

Kit Contents (provides 10 doses of ABRYSVO):  10 vials containing Lyophilized Antigen Component  10 syringes containing Sterile Water Diluent Component  10 vial adaptersAfter reconstitution, a single dose is approximately 0.5 mL.

{ "type": "p", "children": [], "text": "Kit Contents (provides 10 doses of ABRYSVO):  10 vials containing Lyophilized Antigen Component  10 syringes containing Sterile Water Diluent Component  10 vial adaptersAfter reconstitution, a single dose is approximately 0.5 mL." }

Pfizer

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NDC 0069-0344-05Rx only

{ "type": "p", "children": [], "text": "NDC 0069-0344-05Rx only" }

NOTICE: Lyophilized Antigen Component andSterile Water Diluent Component must becombined before use.

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Respiratory SyncytialVirus VaccineABRYSVO®

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For Individuals 60 Years and Older

{ "type": "p", "children": [], "text": "For Individuals 60 Years and Older" }

For Individuals 18 through 59 Years at Increased Riskfor Lower Respiratory Tract Disease caused by RSV

{ "type": "p", "children": [], "text": "For Individuals 18 through 59 Years at Increased Riskfor Lower Respiratory Tract Disease caused by RSV" }

For Pregnant Individuals at 32 through 36 Weeks Gestation

{ "type": "p", "children": [], "text": "For Pregnant Individuals at 32 through 36 Weeks Gestation" }

Kit Contents (provides 5 doses of ABRYSVO):  5 vials containing Lyophilized Antigen Component  5 syringes containing Sterile Water Diluent Component  5 vial adaptersAfter reconstitution, a single dose is approximately 0.5 mL.

{ "type": "p", "children": [], "text": "Kit Contents (provides 5 doses of ABRYSVO):  5 vials containing Lyophilized Antigen Component  5 syringes containing Sterile Water Diluent Component  5 vial adaptersAfter reconstitution, a single dose is approximately 0.5 mL." }

Pfizer

{ "type": "p", "children": [], "text": "Pfizer" }

NDC 0069-0344-01Rx only

{ "type": "p", "children": [], "text": "NDC 0069-0344-01Rx only" }

NOTICE: Lyophilized Antigen Component andSterile Water Diluent Component must becombined before use.

{ "type": "p", "children": [], "text": "NOTICE: Lyophilized Antigen Component andSterile Water Diluent Component must becombined before use." }

Respiratory Syncytial Virus VaccineABRYSVO®

{ "type": "p", "children": [], "text": "Respiratory Syncytial Virus VaccineABRYSVO®\n" }

For Individuals 60 Years and Older

{ "type": "p", "children": [], "text": "For Individuals 60 Years and Older" }

For Individuals 18 through 59 Years at Increased Riskfor Lower Respiratory Tract Disease caused by RSV

{ "type": "p", "children": [], "text": "For Individuals 18 through 59 Years at Increased Riskfor Lower Respiratory Tract Disease caused by RSV" }

For Pregnant Individuals at 32 through 36 Weeks Gestation

{ "type": "p", "children": [], "text": "For Pregnant Individuals at 32 through 36 Weeks Gestation" }

Kit Contents (provides a single dose of ABRYSVO):  1 vial containing Lyophilized Antigen Component  1 syringe containing Sterile Water Diluent Component  1 vial adapterAfter reconstitution, a single dose is approximately 0.5 mL.

{ "type": "p", "children": [], "text": "Kit Contents (provides a single dose of ABRYSVO):  1 vial containing Lyophilized Antigen Component  1 syringe containing Sterile Water Diluent Component  1 vial adapterAfter reconstitution, a single dose is approximately 0.5 mL." }

Pfizer

{ "type": "p", "children": [], "text": "Pfizer" }

NDC 0069-0207-01Rx onlyLyophilized Antigen ComponentNOT TO BE USED ALONEReconstitute with Sterile Water DiluentComponent to form Respiratory Syncytial Virus Vaccine (ABRYSVO®)

{ "type": "p", "children": [], "text": "NDC 0069-0207-01Rx onlyLyophilized Antigen ComponentNOT TO BE USED ALONEReconstitute with Sterile Water DiluentComponent to form Respiratory Syncytial Virus Vaccine (ABRYSVO®)" }

Pfizer Inc.Single dose of approximately0.5 mL after reconstitutionU.S. Lic.No. 2001

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NDC 0069-0250-01

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Sterile Water DiluentComponentNOT TO BE USED ALONE

{ "type": "p", "children": [], "text": "Sterile Water DiluentComponentNOT TO BE USED ALONE" }

Add to 1 vial of LyophilizedAntigen Component toform Respiratory SyncytialVirus Vaccine (ABRYSVO®)U.S. Lic. No. 2001Pfizer Inc.Rx only

{ "type": "p", "children": [], "text": "Add to 1 vial of LyophilizedAntigen Component toform Respiratory SyncytialVirus Vaccine (ABRYSVO®)U.S. Lic. No. 2001Pfizer Inc.Rx only" }

Lot:Exp: OVERPRINT AREA

{ "type": "p", "children": [], "text": "Lot:Exp: OVERPRINT AREA" }

Rx onlyNDC 0069-2465-01

{ "type": "p", "children": [], "text": "Rx onlyNDC 0069-2465-01" }

NOTICE: Lyophilized AntigenComponent and Sterile WaterDiluent Component must becombined before use.

{ "type": "p", "children": [], "text": "NOTICE: Lyophilized AntigenComponent and Sterile WaterDiluent Component must becombined before use." }

Respiratory SyncytialVirus VaccineABRYSVO®

{ "type": "p", "children": [], "text": "Respiratory SyncytialVirus VaccineABRYSVO®\n" }

For Individuals 60 Yearsand Older

{ "type": "p", "children": [], "text": "For Individuals 60 Yearsand Older" }

For Individuals 18 through59 Years at Increased Riskfor Lower Respiratory TractDisease caused by RSV

{ "type": "p", "children": [], "text": "For Individuals 18 through59 Years at Increased Riskfor Lower Respiratory TractDisease caused by RSV" }

For Pregnant Individualsat 32 through 36 WeeksGestation

{ "type": "p", "children": [], "text": "For Pregnant Individualsat 32 through 36 WeeksGestation" }

Contents (provides 1 dose ofABRYSVO): 1 Act-O-Vialcontaining Lyophilized AntigenComponent and Sterile WaterDiluent Component

{ "type": "p", "children": [], "text": "Contents (provides 1 dose ofABRYSVO): 1 Act-O-Vialcontaining Lyophilized AntigenComponent and Sterile WaterDiluent Component" }

After reconstitution, a singledose is 0.5 mL.

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Pfizer

{ "type": "p", "children": [], "text": "Pfizer" }

Rx onlyNDC 0069-2465-10

{ "type": "p", "children": [], "text": "Rx onlyNDC 0069-2465-10" }

NOTICE: Lyophilized Antigen Component and Sterile WaterDiluent Component must be combined before use.

{ "type": "p", "children": [], "text": "NOTICE: Lyophilized Antigen Component and Sterile WaterDiluent Component must be combined before use." }

Respiratory Syncytial Virus VaccineABRYSVO®

{ "type": "p", "children": [], "text": "Respiratory Syncytial Virus VaccineABRYSVO®\n" }

For Individuals 60 Years and Older

{ "type": "p", "children": [], "text": "For Individuals 60 Years and Older" }

For Individuals 18 through 59 Years at Increased Riskfor Lower Respiratory Tract Disease caused by RSV

{ "type": "p", "children": [], "text": "For Individuals 18 through 59 Years at Increased Riskfor Lower Respiratory Tract Disease caused by RSV" }

For Pregnant Individuals at 32 through 36 Weeks Gestation

{ "type": "p", "children": [], "text": "For Pregnant Individuals at 32 through 36 Weeks Gestation" }

Contents (provides 10 doses of ABRYSVO): 10 Act-O-Vials each containingLyophilized Antigen Component and Sterile Water Diluent ComponentAfter reconstitution, a single dose is 0.5 mL.

{ "type": "p", "children": [], "text": "Contents (provides 10 doses of ABRYSVO): 10 Act-O-Vials each containingLyophilized Antigen Component and Sterile Water Diluent ComponentAfter reconstitution, a single dose is 0.5 mL." }

Pfizer

{ "type": "p", "children": [], "text": "Pfizer" }

NDC 0069-2465-19Rx only

{ "type": "p", "children": [], "text": "NDC 0069-2465-19Rx only" }

Act-O-Vial® Respiratory Syncytial Virus VaccineABRYSVO®

{ "type": "p", "children": [], "text": "Act-O-Vial®\nRespiratory Syncytial Virus VaccineABRYSVO®\n" }

Single dose of 0.5 mL afterreconstitutionPfizer Inc.U.S. Lic. No. 2001

{ "type": "p", "children": [], "text": "Single dose of 0.5 mL afterreconstitutionPfizer Inc.U.S. Lic. No. 2001" }