European Commission approves Enflonsia for infants’ first RSV season as Merck reports new SMART data

The European Commission has approved ENFLONSIA™ (clesrovimab) for the prevention of respiratory syncytial virus (RSV) lower respiratory tract disease in neonates and infants during their first RSV season. The approval authorizes the marketing of ENFLONSIA in all 27 European Union member states, as well as Iceland, Liechtenstein and Norway, and is supported by results from the pivotal Phase 2b/3 CLEVER trial and interim data from RSV season 1 of the Phase 3 SMART trial.

ENFLONSIA is a preventive, long-acting monoclonal antibody designed to provide direct, rapid and durable protection through 5 months, a typical RSV season, with non-weight-based dosing. It is the first and only RSV preventive option in the European Union for administration to infants without the need for weight-based dosing. ENFLONSIA is contraindicated for infants with hypersensitivity to the active substance or any of its excipients.

The CLEVER trial was a Phase 2b/3, randomized, double-blind, placebo-controlled, multicenter study to evaluate the efficacy of ENFLONSIA in healthy early and moderate preterm infants and late preterm and full-term infants entering their first RSV season. Participants were randomized 2:1 to receive a 105 mg dose of ENFLONSIA (N=2,412) or saline placebo (N=1,202) by intramuscular injection. The trial met its primary and key secondary endpoints.

The SMART trial evaluates the safety, efficacy and pharmacokinetics of ENFLONSIA versus palivizumab in infants at increased risk for severe RSV disease. The trial enrolled infants at increased risk of severe RSV disease due to prematurity, chronic lung disease of prematurity or hemodynamically significant congenital heart disease entering their first RSV season. In the first RSV season, subjects were assigned in a 1:1 ratio to receive either a 105 mg ENFLONSIA dose or monthly palivizumab administered via intramuscular injection.

New data from the SMART trial in children under 2 years of age who remained at increased risk for severe RSV disease through their second RSV season showed that safety was generally consistent with safety observed in infants who received ENFLONSIA during RSV season 1. In the second season, eligible children under two years with chronic lung disease, congenital heart disease or preterm birth with risk conditions received an open-label 210 mg dose as two 105 mg injections. Among the 276 children treated in the second season, nearly all had chronic lung disease or congenital heart disease.

The monoclonal antibody serum concentrations achieved in children under 2 years of age at increased risk for severe RSV disease through their second RSV season were similar to those in healthy infants in the pivotal Phase 2b/3 CLEVER trial. Results from the SMART study support extrapolation of efficacy to children under 2 years of age at increased risk for severe RSV disease through RSV season 2. The second season results will be shared with the FDA and global regulatory authorities for evaluation for an expanded indication in children at increased risk for severe RSV disease through their second RSV season.

Clinical data from the CLEVER and SMART trials were published in the New England Journal of Medicine in September 2025. ENFLONSIA is approved in the United States, Canada, Switzerland and several other countries for use in infants during their first RSV season, and regulatory filings are underway in additional markets globally. The timing for availability of ENFLONSIA in individual countries will vary by country and depend on multiple factors, including the completion of reimbursement procedures.