New phase 3 data show that Merck’s clesrovimab (Enflonsia) maintained a favorable safety profile and supportive pharmacokinetics in high-risk children under 2 years of age during a second RSV season. The company plans to file for expanded regulatory approval.
Merck has announced positive new findings from the second respiratory syncytial virus (RSV) season of itsphase 3 SMART trial evaluating clesrovimab (Enflonsia) in infants and young children at increased risk for severe RSV disease. The results were presented at RSVVW’26, the 9th conference of the Respiratory Syncytial Virus Foundation (ReSViNET) in Rome, Italy, and will be shared with the FDA and other global regulators.
The SMART trial assessed the safety, efficacy, and pharmacokinetics of Enflonsia across 2 RSV seasons in vulnerable pediatric populations, including children born prematurely and those with chronic lung disease or congenital heart disease. New data focused on children under 2 years of age who remained at increased risk entering their second RSV season and received Enflonsia at the start of that season.
According to Merck, safety outcomes in RSV season 2 were generally consistent with those observed in infants who received clesrovimab during their first RSV season. Importantly, serum concentrations of the monoclonal antibody achieved in these high-risk children were similar to levels seen in healthy infants enrolled in the pivotal phase 2b/3 CLEVER trial, supporting the extrapolation of efficacy to a second RSV season.
Enflonsia showed a consistent safety profile in high-risk children under 2 years of age during a second RSV season.
Pharmacokinetic data support extrapolating efficacy from first-season infants to children entering their second RSV season.
Merck plans to seek expanded regulatory approval to protect vulnerable children beyond their first RSV season.
“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,” Paolo Manzoni, MD, head of Maternal–Infant Medicine at the University of Torino Hospital Degli Infermi and an investigator for the SMART trial, said in a statement. “These new findings from SMART demonstrate the potential of Enflonsia to help protect these vulnerable children, who may require an additional dose for their second RSV season.”
Earlier interim data from RSV season 1 of the SMART trial, together with results from the CLEVER study, supported FDA approval of Enflonsia in June 2025 for infants entering their first RSV season. Those findings were previously presented at IDWeek 2024 and published in The New England Journal of Medicine.
“RSV is among the leading causes of infant hospitalization globally and is especially serious for children under 2 years of age at high risk for severe disease,” Macaya Douoguih, MD, MPH, vice president and Therapeutic Area head of Global Clinical Development at Merck Research Laboratories, said in a statement. “These new data from the SMART study further position Enflonsia as an important potential new option to help protect young children who remain at high risk entering their second RSV season.”
Merck said it plans to submit the second-season results to regulatory authorities to support an expanded indication for children at increased risk of severe RSV disease through their second RSV season. Enflonsia is already approved in the US, Canada, and several other countries for use during the first RSV season, with additional global filings underway.
