Merck Reports Positive Second-Season Data for ENFLONSIA in High-Risk Children

Merck announced positive second RSV season findings from the Phase 3 SMART trial (MK-1654-007) evaluating the safety, efficacy and pharmacokinetics of ENFLONSIA (clesrovimab) in infants and children at increased risk for severe respiratory syncytial virus disease over two RSV seasons. The data were presented during an oral session (Abstract #P455) at RSVVW'26, the 9th conference of the Respiratory Syncytial Virus Foundation (ReSViNET) in Rome, Italy.

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 and received ENFLONSIA at the start of RSV season 2 showed that safety was generally consistent with safety observed in infants who received ENFLONSIA during RSV season 1. 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 (MK-1654-004). 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.

All children who received ENFLONSIA in their second RSV season were at increased risk for severe RSV disease, and nearly all had chronic lung disease or congenital heart disease. The data focused on vulnerable children, most with chronic lung or congenital heart disease, who received the monoclonal antibody at the start of their second RSV season.

Common side effects included irritability, somnolence, and injection-site reactions, with no drug-related serious adverse events reported. The safety profile of ENFLONSIA during the second season remained consistent with observations from the first season and previous studies.

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. ENFLONSIA is currently approved in the United States, Canada and several other countries for use in infants during their first RSV season, and regulatory filings are underway in additional markets globally.

ENFLONSIA, which was FDA-approved in June 2025 for infants entering their first RSV season, is a long-acting monoclonal antibody designed to provide five months of protection with a single dose regardless of weight. The treatment is administered using the same dose regardless of weight (105 mg/0.7 mL in a prefilled syringe) and is designed to provide direct, rapid and durable protection through 5 months, a typical RSV season.

Interim data from RSV season 1 of the Phase 3 SMART trial—alongside data from the pivotal Phase 2b/3 CLEVER trial—supported the FDA approval of ENFLONSIA in June 2025 and subsequent global regulatory approvals. Interim data from RSV season 1 of the SMART trial were also presented at IDWeek 2024 and published in the New England Journal of Medicine. The SMART trial enrolled infants at increased risk of severe RSV disease due to prematurity (<29 weeks through ≤35 weeks gestational age), chronic lung disease of prematurity or hemodynamically significant congenital heart disease entering their first RSV season.