FDA Label for Abrysvo

1 Indications And Usage

ABRYSVO is a vaccine indicated for active immunization for the prevention of lower respiratory tract disease (LRTD) caused by respiratory syncytial virus (RSV) in individuals 60 years of age and older.

2.1 Dose And Schedule

Administer a single dose (approximately 0.5 mL) of ABRYSVO intramuscularly.

2.2 Preparation For Administration

ABRYSVO is supplied in a kit that includes a vial of Lyophilized Antigen Component (a sterile white powder), a prefilled syringe containing Sterile Water Diluent Component and a vial adapter.

Vial of Lyophilized Antigen Component	Syringe of Sterile Water Diluent Component	Vial Adapter
Vial - abrysvo 01

To form ABRYSVO, reconstitute the Lyophilized Antigen Component with the accompanying Sterile Water Diluent Component as described in the panels below.

2.3 Administration

For intramuscular injection only

After reconstitution, 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.

3 Dosage Forms And Strengths

ABRYSVO is a solution for injection. A single dose after reconstitution is approximately 0.5 mL.

4 Contraindications

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)].

5.1 Management Of Acute Allergic Reactions

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

5.2 Syncope

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

5.3 Altered Immunocompetence

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

5.4 Limitations Of Vaccine Effectiveness

Vaccination with ABRYSVO may not protect all vaccine recipients.

6 Adverse Reactions

In clinical trials, the most commonly reported (≥10%) adverse reactions were fatigue (15.5%), headache (12.8%), pain at the injection site (10.5%), and muscle pain (10.1%).

6.1 Clinical Trials Experience

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.

The safety of ABRYSVO was evaluated in Study 1 (NCT05035212) in which 17,215 participants received ABRYSVO and 17,069 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 1 is an ongoing Phase 3, 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 is being conducted in the USA, South Africa, Japan, Canada, Finland, the Netherlands, and Argentina. 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 78% were White, 13% were Black or African American, and 37% 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 7,169 participants (3,630 ABRYSVO participants and 3,539 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.

Other

Solicited Local and Systemic Reactions in Study 1

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

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

Unsolicited Adverse Events in Study 1

Unsolicited adverse events occurring within 1 month after vaccination were similar between groups, reported in 8.9% and 8.5% of participants who received ABRYSVO and placebo, respectively.

Within 30 days after vaccination, atrial fibrillation was reported in 10 vaccine recipients and 4 placebo recipients (of which 4 in the ABRYSVO group and 3 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 1

In Study 1, SAEs were reported by 2.3% of participants in both the ABRYSVO and placebo groups. Three participants in the ABRYSVO group had SAEs which were assessed as possibly related to study vaccination: Guillain-Barre Syndrome reported 7 days after vaccination, Miller Fisher Syndrome reported 8 days after vaccination, and hypersensitivity reported 8 hours after vaccination.

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%. ABRYSVO is not approved for use in individuals younger than 60 years of age.

Data from a clinical trial (NCT04424316) that enrolled pregnant individuals who were randomly assigned 1:1 to receive 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)]) at 24 through 36 weeks’ gestation revealed no evidence for vaccine-associated increase in the risk of congenital anomalies or fetal deaths. In this study, there was a numerical imbalance in preterm births, with more preterm infants born to individuals in the ABRYSVO group compared to individuals in the placebo group (see Human Data).

A developmental and reproductive 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).

Data

Human Data

In a randomized controlled clinical trial (NCT04424316), 3,682 pregnant individuals received ABRYSVO and 3,676 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)]) at 24 through 36 weeks’ gestation. The infant safety population included 3,568 and 3,558 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, 202 (5.7%) and 169 (4.7%), respectively, were born prematurely and 174 (4.9%) and 203 (5.7%), respectively, had reported congenital malformations or anomalies. There were 10 (0.3%) fetal deaths in the ABRYSVO group and 8 (0.2%) in the placebo group.

Animal Data

A developmental toxicity study 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. ABRYSVO is not approved for use in individuals younger than 60 years of age.

Storage After Reconstitution

After reconstitution, administer ABRYSVO immediately or store at room temperature [15°C to 30°C (59°F to 86°F)] and use within 4 hours. Do not store reconstituted vaccine under refrigerated conditions [2°C to 8°C (36°F to 46°F)]. Do not freeze reconstituted vaccine.

Manufactured by
Pfizer Inc.
NY, NY 10001
US License No. 2001

Logo - abrysvo 13

LAB-1498-1.0

8.4 Pediatric Use

The safety and effectiveness of ABRYSVO in individuals younger than 18 years of age have not been established.

8.5 Geriatric Use

ABRYSVO is approved for use in individuals 60 years of age and older. In Study 1, of the 17,215 recipients who received ABRYSVO 62% (n=10,756) were aged 60-69 years of age, 32% (n=5,488) were 70-79 years of age and 6% (n=970) were ≥80 years of age [see Adverse Reactions (6.1) and Clinical Studies (14.1)].

11 Description

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.

After reconstitution, each dose of ABRYSVO is approximately 0.5 mL. The vaccine 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.

The vial stopper and tip cap and rubber plunger of the prefilled syringe are not made with natural rubber latex.

12.1 Mechanism Of Action

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

13.1 Carcinogenesis, Mutagenesis, Impairment Of Fertility

ABRYSVO has not been evaluated for the potential to cause carcinogenicity, genotoxicity, or impairment of male fertility. A developmental and reproductive toxicity study in female rabbits revealed no evidence of impaired female fertility [see Use in Specific Populations (8.1)].

14.1 Efficacy In Individuals 60 Years Of Age And Older

Study 1 is an ongoing 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 are planned to be followed for up to two RSV seasons, approximately 25 months.

Participants were randomized (1:1) to receive ABRYSVO (n=17,197) or placebo (n=17,186). Randomization was stratified by age, 60-69 years (n=21,499, 63%), 70-79 years (n=10,948, 32%), and ≥80 years (n=1,934, 6%). Healthy adults and adults with stable chronic diseases were included. Among enrolled participants 15% 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 1. 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).

Efficacy against Respiratory Syncytial Virus-associated Lower Respiratory Tract Disease

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 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. The median duration of follow-up for efficacy was 7 months.

Vaccine efficacy information is presented in Table 3.

There were 2 cases of RSV associated severe lower respiratory tract disease in the placebo group and no cases in the ABRYSVO group.

16.1 How Supplied

ABRYSVO is supplied in a kit that 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. The Lyophilized Antigen Component is reconstituted with the Sterile Water Diluent Component to form a single dose of ABRYSVO.

ABRYSVO is supplied in cartons of 1, 5, and 10 kits.

The vial stopper and the tip cap and rubber plunger of the prefilled syringe are not made with natural rubber latex.

16.2 Storage And Handling

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.

17 Patient Counseling Information

Prior to administration of this vaccine:

• •Inform vaccine recipient of the potential benefits and risks of vaccination with ABRYSVO.
• •Advise vaccine recipient to report any adverse events to their healthcare provider or to the Vaccine Adverse Event Reporting System at 1-800-822-7967 and www.vaers.hhs.gov.

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

Principal Display Panel - 10 Vial/Syringe Kit Carton

NDC 0069-0344-10
Rx only

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

Respiratory Syncytial
Virus Vaccine
ABRYSVO™

For Intramuscular Use Only
Kit Contents (provides 10 doses of ABRYSVO™):
  10 vials containing Lyophilized Antigen Component
  10 syringes containing Sterile Water Diluent Component
  10 vial adapters
After reconstitution, a single dose of ABRYSVO is
approximately 0.5 mL.

Pfizer

PRINCIPAL DISPLAY PANEL - 10 Vial/Syringe Kit Carton - abrysvo 14

Principal Display Panel - 5 Vial/Syringe Kit Carton

NDC 0069-0344-05
Rx only

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

Respiratory Syncytial
Virus Vaccine
ABRYSVO™

For Intramuscular Use Only
Kit Contents (provides 5 doses of ABRYSVO™):
  5 vials containing Lyophilized Antigen Component
  5 syringes containing Sterile Water Diluent Component
  5 vial adapters
After reconstitution, a single dose of ABRYSVO is
approximately 0.5 mL.

Pfizer

PRINCIPAL DISPLAY PANEL - 5 Vial/Syringe Kit Carton - abrysvo 15

Principal Display Panel - 1 Vial/Syringe Kit Carton

NDC 0069-0344-01
Rx only

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

Respiratory Syncytial
Virus Vaccine
ABRYSVO™

For Intramuscular Use Only
Kit Contents (provides a single dose of ABRYSVO™):
  1 vial containing Lyophilized Antigen Component
  1 syringe containing Sterile Water Diluent Component
  1 vial adapter
After reconstitution, a single dose of
ABRYSVO is approximately 0.5 mL.

Pfizer

PRINCIPAL DISPLAY PANEL - 1 Vial/Syringe Kit Carton - abrysvo 16

Principal Display Panel - 0.5 Ml Vial Label

NDC 0069-0207-01
Rx only
Lyophilized Antigen Component
NOT TO BE USED ALONE
Reconstitute with Sterile Water Diluent
Component to form Respiratory
Syncytial Virus Vaccine (ABRYSVO™)

Pfizer Inc.
Single dose of approximately
0.5 mL after reconstitution
U.S. Lic.
No. 2001

PRINCIPAL DISPLAY PANEL - 0.5 mL Vial Label - abrysvo 17

Principal Display Panel - 1 Syringe Label

NDC 0069-0250-01

Sterile Water Diluent
Component
NOT TO BE USED ALONE

Add to 1 vial of Lyophilized
Antigen Component to
form Respiratory Syncytial
Virus Vaccine (ABRYSVO™)
U.S. Lic. No. 2001
Pfizer Inc.
Rx only

Lot:
Exp:
OVERPRINT
AREA

PRINCIPAL DISPLAY PANEL - 1 Syringe Label - abrysvo 18