Merck Announces European Commission Approval For Enflonsia (Clesrovimab) For Prevention Of Respiratory Syncytial Virus Lower Respiratory Tract Disease In Infants

Merck, known as MSD outside of the United States and Canada, announced that the European Commission (EC) has approved ENFLONSIA (clesrovimab) for the prevention of respiratory syncytial virus (RSV) lower respiratory tract disease in neonates (newborns) and infants during their first RSV season. ENFLONSIA is contraindicated for infants with hypersensitivity to the active substance or any of its excipients. ENFLONSIA is a preventive, long-acting monoclonal antibody (mAb) designed to provide direct, rapid and durable protection through 5 months, a typical RSV season, with non-weight-based dosing.

The EC approval authorizes the marketing of ENFLONSIA in all 27 European Union (EU) member states, as well as Iceland, Liechtenstein and Norway. The timing for availability of ENFLONSIA in individual countries will vary by country and depend on multiple factors, including the completion of reimbursement procedures. The EC approval is supported by results from the pivotal Phase 2b/3 CLEVER trial (MK-1654-004; NCT04767373), which evaluated the safety and efficacy of a single dose of ENFLONSIA administered to preterm and full-term infants (birth to 1 year of age), as well as interim data from RSV season 1 of the Phase 3 SMART trial (MK-1654-007; NCT04938830) evaluating the safety, efficacy and pharmacokinetics of ENFLONSIA versus palivizumab in infants at increased risk for severe RSV disease.

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 CLEVER trial (MK-1654-004; NCT04767373) 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 (=29 to ENFLONSIA also demonstrated a reduction in RSV-associated hospitalizations through 5 months (key secondary endpoint) by 84.2% (95% CI: 66.6, 92.6, p ENFLONSIA was observed to reduce incidence of severe MALRI through 5 months (exploratory endpoint) by 91.7% (95% CI: 62.9, 98.1) (incidence rates: ENFLONSIA, 0.001; placebo, 0.010).

ENFLONSIA was observed to reduce RSV-associated LRI hospitalizations through 5 months (exploratory endpoint) by 90.9% (95% CI: 76.2, 96.5). ENFLONSIA was observed to reduce incidence of RSV-associated MALRI requiring =1 indicator of LRI or severity compared to placebo through 6 months (secondary endpoint) by 59.5% (95% CI: 43.3, 71.1). The trial demonstrated that the safety profile of ENFLONSIA in infants entering their first RSV season was generally comparable to placebo.

As reflected in the SmPC, the most frequent adverse reactions were injection-site pain (6.5%), injection-site erythema (4.4%), injection-site swelling (3.2%) and rash (2.3%). Most (>96%) of the adverse reactions were mild or moderate. The SMART trial (MK-1654-007; NCT04938830) was a Phase 3, randomized, partially-blind, palivizumab-controlled, multicenter study to evaluate the safety, efficacy and pharmacokinetics of ENFLONSIA in infants and children at increased risk for severe RSV disease over two RSV seasons, including early (<29 weeks GA) or moderate preterm infants (=29 to =35 weeks GA) and infants with chronic lung disease of prematurity or congenital heart disease of any GA.