ABRYSVO® Adverse Reactions

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.

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) is an ongoing, 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 3,682 participants received ABRYSVO and 3,675 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 are to be followed for up to 24 months, and infants born in year 2 will be followed for up to 12 months to assess safety. At the time of data evaluation following a median of 8.9 months (range Day 1-23.8 months), 3,568 infants were born to the maternal participants in the ABRYSVO group and 3,558 in the placebo group, and of these, approximately 45.6% have been followed for 12 months. This multicenter study is being 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.

Unsolicited Adverse Events in Study 1

Unsolicited adverse events reported within 1 month after vaccination by maternal participants were 13.7% in the ABRYSVO group and 13.1% 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 6.2% for the placebo group).

Serious Adverse Events in Study 1

In Study 1, serious adverse events in maternal participants were reported by 16.2% in the ABRYSVO group and 15.2% in the placebo group occurring any time during the study (see Table 3) with 4.2% serious adverse events in the ABRYSVO group and 3.7% 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.

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] (202 out of 3,568) in the ABRYSVO group and 4.7% [95% CI: 4.1, 5.5] (169 out of 3,558) in the placebo group. In infants born preterm, 83 infants in the ABRYSVO group and 80 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 4.2% (68/1,631) in the ABRYSVO group and 3.7% (59/1,610) 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 37.1% in the ABRYSVO group compared to 34.5% in the placebo group. Low birth weight was observed in 5.1% of participants in the ABRYSVO group versus 4.4% in the placebo group, and neonatal jaundice was observed in 7.2% in the ABRYSVO group versus 6.7% 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 18,575 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 is an ongoing, 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 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 7,073 participants (3,627 ABRYSVO participants and 3,446 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 4 and 5.

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 10.6% and 10.3% 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 3

In Study 3, SAEs were reported by 3.3% of participants in the ABRYSVO group and 3.2% in the placebo group. 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.

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.

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.