Regulatory Decision Summary for Abrysvo

This Supplemental New Drug Submission (SNDS) is intended for the following clinical safety and efficacy updates:

• Expansion of indication to individuals 18 -59 years of age.

• Concomitant use of Abrysvo with COVID-19 mRNA vaccines and seasonal influenza vaccines.

• Safety updates in healthy pregnant individuals ≤49 years of age.

• Efficacy and safety updates for the older adults ≥60 years of age based on the data at the End of Season (EOS) 1, and EOS 2.

Abrysvo was initially approved for pregnant individuals from 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, and for older adults ≥60 years of age for the prevention of LRTD caused by RSV.

Respiratory syncytial virus (RSV) is a highly contagious human RNA virus of which 2 antigenically distinct subtypes exist (i.e., RSV-A and RSV-B) and that causes respiratory tract infections in people of all ages. Abrysvo currently is indicated for the prevention of lower respiratory tract disease (LRTD) caused by RSV in individuals ≥60 years of age by active immunization. However, there is a significant unmet medical need in individuals 18 through 59 years of age at increased risk of LRTD caused by RSV with underlying comorbidities.

To extend an indication in adults 18 through 59 years of age at increased risk of LRTD caused by RSV, clinical effectiveness of Abrysvo in adults 18 through 59 years of age at increased risk of LRTD was inferred by immunogenicity as compared to the adults ≥60 years of age where efficacy has been demonstrated. Study C3671023 showed that RSV A and RSV B neutralizing responses elicited by Abrysvo in the adults 18 through 59 years of age were noninferior to the adults ≥60 years of age.

Based on the data from in Study C5481001 and Study C3671006 in Adults ≥65 Years of Age, Abrysvo can be co-administered with COVID 19 mRNA vaccine, with or without high dose influenza vaccine, and Abrysvo also can be co-administered with seasonal influenza vaccine (standard dose adjuvanted or high dose unadjuvanted).

Efficacy results for the end of RSV Season 2 analysis for Study C3671013 with an average surveillance duration of 16.36 months were consistent with the End of RSV Season 1 and primary analyses.

No important identified or potential new safety signals were detected for Abrysvo when administered as a single 120 µg dose in 453 adults 18 through 59 years of age at increased risk of LRTD caused by RSV. Safety data from 4,964 healthy participants (most of the pregnant women) 18 through 59 years of age who received Abrysvo 120 µg in the pooled safety database support the evidence.

Abrysvo and BNT162b2 vaccines together or Abrysvo, when coadministered with quadrivalent influenza vaccine (QIV, high dose) or seasonal inactivated influenza vaccine in adults ≥65 years of age was safe and well tolerated. No new safety signals were identified from the updated safety data from C3671008 in the healthy pregnant women ≤49 years of age.

Guillain-Barré syndrome (GBS) is an important potential risk for Abrysvo. In the context of over 7.8 million shipped doses of Abrysvo worldwide, review of all available data, including post-marketing safety data, has not established a causal association with administration of Abrysvo. Healthcare providers are informed of the important risks associated with the use of Abrysvo vaccine, including GBS through the Product Monograph.

An updated Risk Management Plan (RMP) for Abrysvo was reviewed by Health Canada and considered acceptable.

Following review and requested revisions, the final labelling and Product Monograph were considered to be acceptable.

Overall, the benefit-risk profile was favourable for Abrysvo (120 µg) for the approved indication when used under the conditions of use recommended in the approved Product Monograph. Therefore, a Notice of Compliance (NOC) was recommended.

For further details about Abrysvo, please refer to the Product Monograph, approved by Health Canada and available through the Drug Product Database.