Nirsevimab Gets FDA Advisory Committee Recommendation to Prevent RSV in Infants

After an all-day meeting, the Antimicrobial Drugs Advisory Committee (AMDAC) to the US Food and Drug Administration (FDA) voted on June 8 to recommend the approval of nirsevimab (Beyfortus) for the prevention of respiratory syncytial virus (RSV) disease in infants.

Nirsevimab is a long-acting antibody, in development by Sanofi and AstraZeneca, to protect all infants against RSV disease. “Monoclonal antibodies do not require the activation of the immune system to help offer timely, rapid, and direct protection against the disease,” Sanofi previously explained in a statement.

The proposed indication of nirsevimab is to prevent RSV lower respiratory tract disease in neonates and infants born during or entering into their first RSV season. Additionally, the treatment was recommended for children up to 24 months of age who remain vulnerable to severe RSV disease through their second RSV season.

After hearing presentations from AstraZeneca and the FDA, and reviewing all available clinical trial data, AMDAC voted on the following questions:

1. Is the overall benefit-risk assessment favorable for the use of nirsevimab for the prevention of RSV lower respiratory disease in neonates and infants born during or entering their first RSV season?
2. Is the overall benefit-risk assessment favorable for the use of nirsevimab for the prevention of RSV lower respiratory tract disease in children up to 24 months of age who remain vulnerable to severe RSV disease through their second RSV season?

All 21 AMDAC members voted in favor of the first question, and 19 voted in favor of the second, with 2 voting “no.”

Explaining her affirmative vote, Dr. Mary Anne Jackson said, “This is one of the most important infectious diseases affecting the pediatric population.” She also noted her recommendation was informed by good safety and efficacy data for nirsevimab. Several other AMDAC voting members voiced their support for how well the study was designed, with clear endpoints.

Some of the most promising trial data came from the HARMONIE phase 3b study, which recruited more than 8000 infants under 12 months of age across Germany, France, and the United Kingdom. The investigators compared a single intramuscular dose of nirsevimab (<5 kg 50 mg; ≥5 kg 100 mg) to no intervention, and found nirsevimab reduced hospitalizations due to severe RSV-related LRTD by 83.21%.

Additional data from the HARMONIE trial suggest nirsevimab reduced the incidence of hospitalizations due to severe RSV-related LRTD, defined by requiring oxygen supplementation, by 75.71%. Nirsevimab also reduced all-cause LRTD hospitalization by 58.04% compared to infants who received no intervention. Throughout the HARMONIE trial, and into the 12-month follow-up period, nirsevimab maintained a favorable safety profile.

The FDA will take AMDAC’s recommendation into serious consideration before deciding to approve nirsevimab. Nirsevimab's Prescription Drug User Fee Act (PDUFA) date, the FDA target action date for their decision, is in the third quarter of 2023. If approved, the US Centers for Disease Control and Prevention (CDC) will make a separate authorization decision.