FDA Accepts Enflonsia sBLA for RSV Prevention in High-Risk Children During Their Second RSV Season – Merck
Merck announced that the FDA has accepted a supplemental Biologics License Application (sBLA) for Enflonsia (clesrovimab-cfor) to expand its indication to include prevention of respiratory syncytial virus (RSV) lower respiratory tract disease (LRTD) in children under two years of age at increased risk for severe RSV disease through their second RSV season.
The FDA has set a Prescription Drug User Fee Act (PDUFA), or target action, date of March 22, 2027.
In July 2026, the European Medicines Agency (EMA) accepted the application to expand marketing authorization for Enflonsia in the European Union (EU) for the same population.
Enflonsia was approved by the U.S. FDA in June 2025 and by the European Commission in April 2026 for the prevention of RSV LRTD in infants born during or entering their first RSV season. Enflonsia is the first and only preventive option against RSV LRTD administered to infants without the need for weight-based dosing.
“For some children, the potentially serious impact of RSV does not stop after their first RSV season. The recent FDA and EMA regulatory filings represent important opportunities to help expand protection with Enflonsia for vulnerable children under two years of age during their second RSV season – potentially further reducing the significant burden of RSV on families and health care systems.” – Dr. Macaya Douoguih, vice president, Therapeutic Area Head, Global Clinical Development, Merck Research Laboratories.
Even with protection during their first RSV season, certain children – including those born with chronic lung disease, congenital heart disease or early or moderate preterm birth with certain risk conditions – remain vulnerable to severe RSV disease during their second RSV season.
Both the U.S. and EU applications are supported by data from the Phase 3 SMART trial (MK-1654-007), which were presented at RSVVW’26, the 9th conference of the Respiratory Syncytial Virus Foundation (ReSViNET), in February 2026 and published in the New England Journal of Medicine in September 2025 *(interim RSV season 1 results) and JAMA Pediatrics in July 2026 (full results).
Enflonsia is approved in more than 40 countries worldwide, including the United States, Canada, the European Union, China and Japan, for use in infants during their first RSV season. Regulatory filings are underway for approval in additional countries globally, as well as for indication expansion where already approved.
About the Phase 3 SMART Trial
The SMART trial (MK-1654-007) (NCT04938830) was a Phase 3, randomized, partially-blind, palivizumab-controlled, multicenter study to evaluate the safety, efficacy and pharmacokinetics of Enflonsia in infants and children at increased risk for severe RSV disease over two RSV seasons. The trial enrolled early (<29 weeks gestational age [GA]) or moderate preterm infants (≥29 to ≤35 weeks GA) and infants with chronic lung disease (CLD) of prematurity or congenital heart disease (CHD) of any GA.
In RSV season 1, participants were randomized 1:1 to receive either a 105 mg dose of Enflonsia (n=502) or monthly palivizumab (n=501) by intramuscular (IM) injection. In RSV season 2, eligible participants (children under 2 years of age with CLD, CHD or early or moderate preterm birth with certain risk conditions) received an additional open-label 210 mg dose of Enflonsia by IM injection (n=276, of whom 138 received Enflonsia and 138 received palivizumab in RSV season 1). Nearly all participants (99%) who received Enflonsia in RSV season 2 had CLD (n=229) or CHD (n=43).
