FDA Approves Nirsevimab for RSV in Infants

Today, the FDA approved Sanofi and AstraZeneca’s nirsevimab-alip (Beyfortus) for the prevention of respiratory syncytial virus (RSV) lower respiratory tract disease (LRTD) in newborns and infants born during or entering their first RSV season, and for children up to 24 months of age who remain vulnerable to severe RSV disease through their second RSV season.

“RSV can cause serious disease in infants and some children and results in a large number of emergency department and physician office visits each year,” John Farley, MD, MPH, director of the Office of Infectious Diseases in the FDA’s Center for Drug Evaluation and Research, said in a statement. “Today’s approval addresses the great need for products to help reduce the impact of RSV disease on children, families and the health care system.”

Nirsevimab is a single-dose long-acting monoclonal antibody provided directly to newborns and infants as a single dose, and offers rapid protection to help prevent LRTD caused by RSV, without requiring activation of the immune system. The administration can be timed to the start of the RSV season.

The FDA's Antimicrobial Drugs Advisory Committee (AMDAC) voted to recommend the approval of nirsevimab last month.

What the Data Showed
The phase 3 MELODY trial (Trial 04) was a randomized, double-blind, placebo-controlled trial conducted across 21 countries designed to determine the safety and efficacy of nirsevimab against medically attended LRTD caused by RSV in healthy term and late preterm infants (35 weeks gestational age or greater) entering their first RSV season, including efficacy against severe disease such as hospitalization, through 150 days after dosing. The primary endpoint was met, reducing the incidence of medically attended RSV LRTD by 74.9% (95% CI 50.6, 87.3; P<0.001) compared to placebo. The efficacy of nirsevimab against the secondary endpoint of hospitalization was 60.2% (95% CI: -14.6, 86.2).

As previously reported in Contagion, additional trial data came from the HARMONIE phase 3b study. This trial 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.

What’s Next
Sanofi and AstraZeneca plan to make the monoclonal antibody available in the United States ahead of the upcoming 2023-2024 RSV season.

“Beyfortus is the only monoclonal antibody approved for passive immunization to provide safe and effective protection for all infants during their first RSV season,” Thomas Triomphe, executive vice president, Vaccines, Sanofi, said in a statement. “I am proud that, by prioritizing this potential game-changer, we are now about to bring Beyfortus to American families.”