FDA Accepts Merck Application to Expand ENFLONSIA Protection Into Second RSV Season

For infection prevention and pediatric health professionals, respiratory syncytial virus (RSV) remains one of the leading causes of hospitalization among infants and young children. Although recent advances in RSV prevention have significantly reduced disease during the first RSV season, certain children continue to face elevated risk as they enter their second season. Now, Merck is seeking to extend protection for that vulnerable population.

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 RSV lower respiratory tract disease (LRTD) in children younger than 2 years who remain at increased risk for severe RSV disease during their second RSV season. The European Medicines Agency (EMA) has also accepted a similar application for review.

The FDA has assigned a Prescription Drug User Fee Act (PDUFA) target action date of March 22, 2027.

Why a Second RSV Season Matters

While many healthy infants experience declining RSV risk after their first year of life, children with chronic lung disease of prematurity, congenital heart disease, or those born very preterm may continue to be susceptible to severe RSV illness beyond infancy.

"For some children, the potentially serious impact of RSV does not stop after their first RSV season," said Macaya Douoguih, MD, vice president and therapeutic area head of Global Clinical Development at Merck Research Laboratories. "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."

Evidence Supporting the Application

The regulatory submissions are supported by data from the Phase 3 SMART trial, a multicenter, randomized study evaluating the safety, efficacy, and pharmacokinetics of ENFLONSIA in infants and young children at elevated risk for severe RSV disease across 2 RSV seasons. Results from the study were recently published in JAMA Pediatrics after earlier interim findings appeared in the New England Journal of Medicine.

The study enrolled infants born before 29 weeks' gestation, moderately preterm infants, and children with chronic lung disease or congenital heart disease. Eligible participants entering their second RSV season received an additional dose of ENFLONSIA, with nearly all participants in the second-season cohort having chronic lung disease or congenital heart disease.

Implications for Infection Prevention

Although RSV prevention is often associated with pediatricians and neonatologists, infection preventionists also play an important role in reducing RSV transmission throughout hospitals and outpatient facilities. Annual RSV seasons can strain pediatric units, increase hospital admissions, and contribute to health care-associated respiratory virus transmission among vulnerable patients.

Expanding preventive options for children who remain at elevated risk beyond infancy could help reduce severe RSV disease, potentially lowering hospitalizations and easing seasonal pressure on pediatric health care systems.

ENFLONSIA was initially approved by the FDA in 2025 for newborns and infants entering their first RSV season and is now approved in more than 40 countries. Unlike weight-based monoclonal antibodies, ENFLONSIA uses a single fixed-dose administration designed to provide protection throughout a typical 5-month RSV season.

As RSV prevention strategies evolve alongside maternal vaccination and monoclonal antibody options, infection prevention professionals will likely continue to monitor how expanded indications influence pediatric hospitalization trends, resource utilization, and seasonal respiratory virus prevention efforts.

If approved, the expanded indication would provide another option for protecting children who remain vulnerable to severe RSV disease beyond their first year of life. Until then, the FDA's review will continue through early 2027.