Abrysvo

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.

Pharmacology: Mechanism of Action: Active Immunization: ABRYSVO induces an immune response against RSV preF 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.
Pharmacodynamics: Clinical Studies: Study in Pregnant Individuals For Efficacy in Their Infants from Birth Through 6 Months of Age: 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]). 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 under Adverse Reactions.
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 1 to 5. (See Tables 1, 2, 3, 4 and 5.)

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Efficacy in Individuals 60 Years of Age and Older: 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 6. (See Table 6.)

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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 and second RSV seasons and combined across the two RSV seasons are presented in Table 7. Vaccine efficacy is maintained through two RSV seasons. At the end of the second RSV season, subgroup analyses of VE by age, pre-specified significant underlying conditions, and RSV A and RSV B subgroups in ABRYSVO recipients were consistent with the main analyses and support consistent VE across different age and risk groups. (See Table 7.)

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Immunogenicity in Individuals 18 Through 59 Years of Age: Study 4 (NCT05842967) 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 an 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 Clinical Trials Experience under Adverse Reactions]. 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 8 and 9). 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 8), 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 9). (See Tables 8 and 9.)

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Concomitant Administration of ABRYSVO with a Seasonal Inactivated Influenza Vaccine: In Study 5 (NCT05301322) [see Clinical Trials Experience under Adverse Reactions], 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).
Concomitant Administration of ABRYSVO with a COVID-19 mRNA Vaccine or ABRYSVO with a COVID-19 mRNA Vaccine and with a High Dose Influenza Vaccine: In Study 6 (NCT05886777) [see Clinical Trials Experience under Adverse Reactions], antibody responses to antigens contained in ABRYSVO, COMIRNATY, and FLUZONE HD 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 COMIRNATY compared to individual administration. The lower limit of the 2-sided 97.5% CI for the GMR for RSV A and RSV B NTs and both SARS-CoV-2 Omicron BA.4/BA.5 strain and reference strain met the predefined 2-fold non-inferiority criterion.
Immunologic non-inferiority was also demonstrated for concomitant administration of ABRYSVO, COMIRNATY, and FLUZONE HD compared to each individual administration. The lower limit of the 2-sided 97.5% CI for the GMR for RSV A and RSV B NTs, both SARS-COV-2 Omicron BA.4/BA.5 strain and reference strain, and each of the four strain (H1N1 A/Victoria, H3N2 A/Darwin, B/Austria, B/Phuket) specific HAI titers met the predefined 2-fold non-inferiority criterion.
Concomitant Administration of ABRYSVO with Tetanus Toxoid, Reduced Diphtheria Toxoid and Acellular Pertussis Vaccine, Adsorbed: Study 7 (NCT04071158) 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) 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 Interactions].
Toxicology: Nonclinical Toxicology: Carcinogenesis, Mutagenesis, Impairment of Fertility: 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 Pregnancy under Use in Pregnancy & Lactation].

Immunization of Pregnant Individuals: 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.
Immunization of 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 60 years of age and older.
Immunization of Individuals 18 through 59 Years of Age: 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.

Dose and Schedule: Administer a single dose (approximately 0.5 mL) of ABRYSVO intramuscularly.
Preparation for Administration: The lyophilized vaccine (powder) must be reconstituted only with the diluent provided to form ABRYSVO.
Step 1. Attach vial adapter: Peel off the top cover from the vial adapter packaging and remove the flip off cap from the vial.
While keeping the vial adapter in its packaging, center over the vial's stopper and connect with a straight downward push. Do not push the vial adapter in at an angle as it may result in leaking. Remove the packaging.
Step 2. Reconstitute lyophilized vaccine component to form ABRYSVO: For all syringe assembly steps, hold the syringe only by the Luer lock adapter. This will prevent the Luer lock adapter from detaching during use.
Twist to remove the syringe cap, then twist to connect the syringe to the vial adapter. Stop turning when resistance is felt.
Inject the entire contents of the syringe into the vial. Hold the plunger rod down and gently swirl the vial until the powder is completely dissolved. Do not shake.
Step 3. Withdraw reconstituted vaccine: Invert the vial completely and slowly withdraw the entire contents into the syringe to ensure a 0.5 mL dose of ABRYSVO.
Twist to disconnect the syringe from the vial adapter.
Attach a sterile needle suitable for intramuscular injection.
Reconstituted Vaccine for Administration: The prepared vaccine is a clear and colorless solution. Visually inspect the vaccine for large particulate matter and discoloration prior to administration. Do not use if large particulate matter or discoloration is found.
Disposal: Any unused medicinal product or waste material should be disposed of in accordance with local requirements.
Administration: For intramuscular injection only.
After reconstitution, administer ABRYSVO immediately or store at room temperature (15°C to 30°C) and use within 4 hours. Discard reconstituted vaccine if not used within 4 hours.

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

Guillain-Barré Syndrome: 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 Postmarketing Experience under Adverse Reactions].
Potential Risk of Preterm Birth: A numerical imbalance in preterm births in ABRYSVO recipients was observed compared to placebo recipients in two clinical studies [see Clinical Trials Experience under Adverse Reactions]. 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.
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.
Syncope: Syncope (fainting) may occur in association with administration of injectable vaccines, including ABRYSVO. Procedures should be in place to avoid injury from fainting.
Altered Immunocompetence: Immunocompromised individuals, including those receiving immunosuppressive therapy, may have a diminished immune response to ABRYSVO.
Limitations of Vaccine Effectiveness: Vaccination with ABRYSVO may not protect all vaccine recipients.
Use in Pregnancy & Lactation: See USE IN PREGNANCY & LACTATION section for further information.
Use in Children: The safety and effectiveness of ABRYSVO to prevent RSV-associated lower respiratory tract disease (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.
Use in the Elderly: 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 Clinical Trials Experience under Adverse Reactions and Pharmacology: Pharmacodynamics: Clinical Studies: Efficacy in Individuals 60 Years of Age and Older under Actions].

Pregnancy: 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]) 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 Potential Risk of Preterm Birth under Precautions, Clinical Trials Experience under Adverse Reactions, Clinical Considerations as follows, Data as follows and Pharmacology: Pharmacodynamics: Clinical Studies: Study in Pregnant Individuals For Efficacy in Their Infants from Birth Through 6 Months of Age under Actions].
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 as follows).
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 Clinical Trials Experience under Adverse Reactions].
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 Potential Risk of Preterm Birth under Precautions, Clinical Trials Experience under Adverse Reactions and Pharmacology: Pharmacodynamics: Clinical Studies: Study in Pregnant Individuals For Efficacy in Their Infants from Birth Through 6 Months of Age under Actions]. 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 Clinical Trials Experience under Adverse Reactions]. 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 14 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]. 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.
Lactation: 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.

In pregnant individuals, the most commonly reported (≥10%) adverse reactions were pain at the injection site (40.7%), headache (31.0%), muscle pain (26.6%), and nausea (20.0%).
In individuals 60 years of age and older, the most commonly reported (≥10%) adverse reactions were fatigue (15.7%), headache (12.9%), pain at the injection site (10.6%), and muscle pain (10.2%).
In individuals 18 through 59 years of age with chronic medical conditions, the most commonly reported (≥10%) adverse reactions and for which the rate for ABRYSVO exceeds the rate for placebo were pain at the injection site (35.3%), muscle pain (24.4%), joint pain (12.4%), and nausea (11.8%).
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.
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, pre-eclampsia, 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]). 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 Immunization of Pregnant Individuals under Indications/Uses]. 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 Immunization of Pregnant Individuals under Indications/Uses].
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 10 and 11. (See Tables 10 and 11.)

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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 (7.1% for the ABRYSVO group versus 6.3% for the placebo group). Within 14 days of vaccination, lymphadenopathy was reported in 2 vaccine recipients and 0 placebo recipients.
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 12) 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. (See Table 12.)

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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]). 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.
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 13 and 14. (See Tables 13 and 14.)

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Click on icon to see table/diagram/image

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. Within 14 days of vaccination, lymphadenopathy was reported in 6 vaccine recipients and 3 placebo recipients. 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, two cases of variants of Guillain-Barré syndrome (chronic idiopathic demyelinating polyneuropathy reported 7 days after vaccination and Miller Fisher syndrome reported 8 days after vaccination) and one case of hypersensitivity reported 8 hours after vaccination.
Individuals 18 through 59 Years of Age: 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]). 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 Pharmacology: Pharmacodynamics: Clinical Studies: Immunogenicity in Individuals 18 Through 59 Years of Age under Actions]. 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 15 and 16. (See Tables 15 and 16.)

Click on icon to see table/diagram/image


Click on icon to see table/diagram/image

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.
Serious Adverse Events Reported from Other Studies: Anaphylaxis was reported in a participant enrolled in a study in the US, with onset of symptoms 10 minutes after vaccination with ABRYSVO.
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.
Concomitant Administration of ABRYSVO with a COVID-19 mRNA Vaccine or ABRYSVO with a COVID-19 mRNA Vaccine and with a High Dose Influenza Vaccine: Study 6 (NCT05886777) was a Phase 1/2, randomized, multicenter, parallel group, observer-blinded study conducted in the US in healthy individuals ≥65 years of age. Study objectives included safety and assessing interference in the immune response of ABRYSVO concomitantly administered with COMIRNATY, and assessing interference in the immune response of concomitant use of ABRYSVO, COMIRNATY, and FLUZONE HD.
Solicited local and systemic reactions and adverse events for the concomitantly administered vaccines were similar to those observed for the respective individual vaccines. Within 7 days following vaccine administration, pain at the injection site was reported by 56.7% of participants who received ABRYSVO administered concomitantly with COMIRNATY (n=157) and 53.8% of participants who received ABRYSVO administered concomitantly with COMIRNATY and FLUZONE HD (n=158), compared to 10.5%, 62.7%, and 51.7% who received each of the vaccines individually (ABRYSVO n=152, COMIRNATY n=150, FLUZONE HD n=149). Fatigue was reported by 38.9% of participants who received ABRYSVO administered concomitantly with COMIRNATY and 46.8% of participants who received ABRYSVO administered concomitantly with COMIRNATY and FLUZONE HD, compared to 24.3%, 35.3%, and 28.9% who received each of the vaccines individually. There were no other notable differences in reported solicited local and systemic adverse reactions within 7 days following ABRYSVO administered concomitantly with COMIRNATY with or without FLUZONE HD compared to ABRYSVO administered alone. No SAEs were considered related to vaccination.
Postmarketing Experience: 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.
Immune System Disorders: Hypersensitivity reactions including rash and urticaria.
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 analyse 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 7 (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 Pharmacology: Pharmacodynamics: Clinical Studies: Concomitant Administration of ABRYSVO with Tetanus Toxoid, Reduced Diphtheria Toxoid and Acellular Pertussis Vaccine, Adsorbed under Actions].
Concomitant administration of Tdap with ABRYSVO in pregnant individuals has not been studied.

Storage Before Reconstitution: Store refrigerated at 2°C to 8°C 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 (15°C to 30°C) and use within 4 hours. Do not freeze reconstituted vaccine.

Prior to administration of this vaccine: Inform vaccine recipient of the potential benefits and risks of vaccination with ABRYSVO.

Vaccines, Antisera & Immunologicals

J07BX05 - respiratory syncytial virus vaccines ; Belongs to the class of other viral vaccines. Used for active immunization against respiratory syncytial virus.

POM