Regulatory Decision Summary for Abrysvo (Respiratory Syncytial Virus Stabilized Prefusion F Subunit Vaccine)

The purpose of this new drug submission (NDS) was seek market authorization of Abrysvo for the prevention of lower respiratory tract disease (LRTD) caused by respiratory syncytial virus (RSV).

After evaluation of the submitted data package, Health Canada authorized Abrysvo for:

1. Active immunization of pregnant individuals from 32 through 36 weeks gestational age for the prevention of LRTD and severe LRTD caused by RSV in infants from birth through 6 months of age.

2. Active immunization for the prevention of LRTD caused by RSV in adults 60 years of age and older.

Respiratory syncytial virus (RSV) infection is a major cause of lower respiratory illness in people of all ages, particularly among older adults and infants. At present there is no vaccine available in Canada to prevent RSV in infants and children.

The authorization for maternal vaccination was supported by the clinical data generated in a randomized, double-blinded, placebo-controlled Phase 3 study designed to evaluate the efficacy and safety of maternal immunization with Abrysvo against RSV-associated lower respiratory track disease (LRTD) in infants. The study enrolled healthy pregnant women ≤49 years of age who were between 24 and 36 weeks of gestation. In this study maternal participants were randomised (1:1 ratio) to receive a single dose of Abrysvo (n = 3,695) or placebo (n = 3,697).

The efficacy of Abrysvo was demonstrated for prevention of RSV-associated lower respiratory tract disease (RSV-LRTD) and severe LRTD in infants from birth through 6 months of age by active immunization of pregnant individuals. Abrysvo reduced the risk of developing RSV- associated severe LRTD by 69.4% in infants within 180 days after birth when the pregnant individuals were immunized.

Abrysvo elicited neutralizing antibodies (nAb) against RSV A and RSV B in the vaccinated pregnant individuals one month after vaccination. The neutralizing antibodies were observed in infants after birth with maternal vaccination.

The efficacy data for older adults 60 years of age and older were collected from 32,614 participants (16,306 in the Abrysvo group and 16,308 in the placebo group, and 76.9% of the participants in the Abrysvo group and 76.6% of the participants in the placebo groups completed the 6-month safety follow-up visit. The efficacy of Abrysvo was demonstrated for prevention of RSV-associated lower respiratory tract disease (RSV-LRTD) with at 2 of 5 symptoms (cough, wheezing, sputum, shortness of breath, and tachypnea) and prevention of RSV-LRTD with at least 3 symptoms. With a single dose of Abrysvo 120 µg in adults ≥60 years of age, the vaccine efficacy for LRTI-RSV cases with at least 2 was 66.7%, and for LRTI-RSV cases with at least 3 symptoms was 85.7%.

Abrysvo elicited neutralizing antibodies (nAb) against RSV A and RSV B older adults 60 years of age and older one month after vaccination. RSV A– and RSV B– nAb GMFRs remained 4- to 5-fold higher at 12 months after vaccination compared to before vaccination.

Abrsyvo was considered safe in pregnant individuals ≤49 years of age, based on assessment of post-vaccination reactions in the first 7 days, other adverse events (AEs) in the first 28 days, and adverse events of special interest or AESIs (e.g., premature delivery and pre-eclampsia) and serious adverse reactions including deaths in the first 6 months. The most common adverse reaction following Abrysvo vaccination was fatigue (46.1%), followed by injection site pain (40.6%), headaches (31.0%), and myalgias (26.6%) with no worrisome patterns.

For infants born to immunized mothers, Abrysvo was considered safe based on assessment of adverse events (AEs) in the first 28 days following birth, and AESIs (e.g., premature birth and low weight birth) and serious adverse reactions including deaths in the first 12-24 months. There was a numerical imbalance of prematurity among infants born to maternal participants immunized with Abrysvo vs. placebo during the less than 32 weeks gestational period. As a precaution, the indication for Abrysvo is currently limited to 32 through 36 weeks gestation in maternal participants.

Abrysvo was considered safe in adults 60 years and older for the prevention of LRTI by RSV based on assessment of 17,215 participants. Common side effects, such as fatigue, headache, injection site pain, and muscle pain, were generally mild to moderate and occurred within the first 7 days post-vaccination. Serious adverse events included Guillain-Barre Syndrome (GBS), Miller Fisher Syndrome (MFS), and hypersensitivity reactions (1 case), but it is not clear if GBS and MFS were related to Abrysvo or not. More people in the Abrysvo group had atrial fibrillation compared to the non-Abrysvo group, however it is unclear if this is a finding by chance, or if there is a relationship to Abrysvo. A further study will be conducted to assess this further.

Based on the currently available efficacy, immunogenicity and safety evidence, the benefit/risk profile of Abrysvo administered as a single dose in a population of pregnant individuals ≤49 YOA during 32 through 36 weeks gestation, as well as in a population of adults ≥60 YOA is favorable.

The recommended dose is 120 µg of RSV stabilized prefusion F protein (60 mcg Subgroup A and 60 mcg Subgroup B antigens) as a single 0.5 mL dose.

Data on vaccine efficacy are currently limited to approximately 6 months post-vaccination; therefore, there is no information on long-term protection by Abrysvo.

Data in multiple pregnancies or booster doses are not currently available.

The data for individuals older than 80 years of age are limited. Data in high-risk immuno-compromised populations are not currently available.