FDA will review Enflonsia’s ability to protect high-risk children under 2 years of age during their second RSV season.
RT’s Three Key Takeaways:
- Regulatory Review: The FDA accepted a supplemental Biologics License Application (sBLA) for Enflonsia to protect high-risk children under 2 years of age during their second respiratory syncytial virus (RSV) season, setting a target action date of March 22, 2027.
- Expanded Patient Eligibility: If approved, vulnerable young children diagnosed with chronic lung disease (CLD), congenital heart disease (CHD), or qualifying preterm birth conditions would be eligible to receive a second-season dose.
- Clinical Trial Foundation: The application is supported by findings from the phase 3 SMART trial, which evaluated the antibody’s safety, efficacy, and pharmacokinetics against palivizumab over two consecutive seasons.
The FDA has accepted a supplemental Biologics License Application (sBLA) for Merck’s Enflonsia (clesrovimab-cfor) to expand its indication to include prevention of respiratory syncytial virus (RSV) lower respiratory tract disease (LRTD) in children under 2 years of age who remain at increased risk for severe disease during their second RSV season, according to the company.
The agency set a Prescription Drug User Fee Act (PDUFA) target action date of March 22, 2027, the company announced. In addition, the European Medicines Agency (EMA) accepted an application in July 2026 to expand marketing authorization for the same pediatric population across the European Union (EU).
The US FDA initially approved Enflonsia in June 2025, and the European Commission granted approval in April 2026 for the prevention of RSV LRTD in infants born during or entering their first RSV season. The preventative monoclonal antibody is the first and only option against RSV LRTD administered to infants without requiring weight-based dosing, according to Merck.
If the supplemental application receives approval, children under 2 years of age at elevated risk for severe disease will be eligible to receive an additional dose of Enflonsia for their second season.
“For some children, the potentially serious impact of RSV does not stop after their first RSV season,” said Dr Macaya Douoguih, vice president, therapeutic area head, global clinical development, Merck Research Laboratories, in a news release. “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 healthcare systems.”
Persistent Vulnerability in High-Risk Toddlers
Even when protected throughout their initial RSV season, certain pediatric patient populations remain susceptible to severe infection during their second year of life, including children born with chronic lung disease (CLD), congenital heart disease (CHD), or early or moderate preterm birth with specific risk conditions, according to the manufacturer.
The regulatory submissions in both the US and the EU rely on data generated from the phase 3 SMART trial (MK-1654-007). Trial findings were presented at RSVVW’26, the 9th conference of the Respiratory Syncytial Virus Foundation, in February 2026. Interim results for the first season appeared in the New England Journal of Medicine in September 2025, and full trial findings were published in JAMA Pediatrics in July 2026.
Phase 3 SMART Trial Design
According to clinical trial details released by Merck, the SMART trial was a randomized, partially-blind, palivizumab-controlled, multicenter investigation assessing the safety, efficacy, and pharmacokinetics of Enflonsia across two consecutive RSV seasons.
The study enrolled early preterm infants born at less than 29 weeks gestational age (GA), moderate preterm infants born between 29 and 35 weeks GA, and infants of any gestational age diagnosed with CLD of prematurity or CHD.
During the first RSV season, 1,003 participants were randomized 1:1 to receive either a single 105 mg intramuscular (IM) injection of Enflonsia (n=502) or monthly palivizumab IM injections (n=501).
In the second RSV season, 276 eligible children under 2 years of age with CLD, CHD, or early or moderate preterm birth with qualifying risk factors received an open-label 210 mg IM dose of Enflonsia. Of those 276 children, 138 had received Enflonsia and 138 had received palivizumab during their first season. Nearly all second-season recipients (99%) had underlying CLD (n=229) or CHD (n=43).
Enflonsia is currently approved in more than 40 countries, including the US, Canada, the EU, China, and Japan, for use in infants during their first RSV season, with additional international regulatory filings and indication expansions underway.
