FDA Reviews Clesrovimab for Second-Season RSV Prevention in High-Risk Children

The US Food and Drug Administration (FDA) has accepted a supplemental biologics license application (sBLA) seeking to expand clesrovimab-cfor (Enflonsia) for prevention of respiratory syncytial virus (RSV) lower respiratory tract disease (LRTD) in children younger than 2 years who remain at increased risk during their second RSV season. The agency set a March 22, 2027, Prescription Drug User Fee Act target date.¹

“For some children, the potentially serious impact of RSV does not stop after their first RSV season,” Macaya Douoguih, MD, vice president and therapeutic area head of global clinical development at Merck Research Laboratories, said in a statement.¹ The European Medicines Agency accepted an application for the same population in July 2026.

Acceptance of the applications begins regulatory review and does not establish that clesrovimab is effective or approved for second-season prophylaxis. The submissions are supported by the phase 3 SMART trial (NCT04938830), a randomized, partially blinded, multicenter study comparing clesrovimab with palivizumab in infants and children at increased risk for severe RSV disease.²

The trial enrolled infants born at less than 29 weeks’ gestation or between 29 and 35 weeks’ gestation, as well as infants with chronic lung disease of prematurity or congenital heart disease. During the first RSV season, 1003 participants were randomly assigned 1:1 to a single 105-mg intramuscular dose of clesrovimab or monthly intramuscular palivizumab.¹

For the second season, 276 eligible children younger than 2 years received an open-label 210-mg dose of clesrovimab. Half had received clesrovimab during the first season and half had received palivizumab. Nearly all second-season recipients had chronic lung disease (n = 229) or congenital heart disease (n = 43), limiting the available evidence for other risk groups included in the proposed indication.¹

Clesrovimab is an extended half-life monoclonal antibody that provides passive immunization. The FDA approved a fixed 105-mg dose in June 2025 for newborns and infants born during or entering their first RSV season; the European Commission approved the first-season indication in April 2026.¹ The proposed second-season regimen uses a higher 210-mg dose.

For the currently approved US indication, the most frequently reported adverse reactions are injection-site erythema (3.8%), injection-site swelling (2.7%), and rash (2.3%). The product is contraindicated in infants with previous serious hypersensitivity to any component. It may also interfere with rapid antigen-based RSV assays, for which confirmatory reverse-transcription polymerase chain reaction testing may be appropriate when clinical suspicion remains high.¹

The FDA review will need to clarify second-season efficacy, adverse-event rates, subgroup consistency, and how a single clesrovimab dose compares with monthly palivizumab. Generalizability beyond children with chronic lung or congenital heart disease also remains uncertain.

References

1. Merck & Co, Inc. U.S. FDA accepts sBLA for ENFLONSIA (clesrovimab-cfor) to update its respiratory syncytial virus lower respiratory tract disease indication. Published August 6, 2026. https://www.businesswire.com/news/home/20260805331090/en/U.S.-FDA-Accepts-sBLA-for-ENFLONSIA-clesrovimab-cfor-to-Update-its-Respiratory-Syncytial-Virus-RSV-Lower-Respiratory-Tract-Disease-Indication-to-Include-Children-Under-Two-Years-at-Increased-Risk-for-Severe-RSV-for-Their-Second-Season
2. ClinicalTrials.gov. Study of clesrovimab in infants and children at increased risk for severe RSV disease (SMART; NCT04938830). https://clinicaltrials.gov/study/NCT04938830