Clesrovimab Wins FDA Approval for Prevention of RSV LRTD in Infants During First RSV Season

The FDA on Monday June 9 approved clesrovimab-cfor for the prevention of respiratory syncytial virus (RSV) lower respiratory tract disease in neonates and infants entering their first RSV season, according to an announcement from Merck. To be marketed as Enflonsia, the long-acting monoclonal antibody is administered as a single 105 mg intramuscular dose, regardless of an infant's weight, with protection demonstrated to last through a typical 5-month RSV season.1

The approval marks the first non-weight-based RSV preventive monoclonal antibody available for this population, Merck stated.1

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RSV is the leading cause of infant hospitalization in the United States, and severe infections can result in bronchiolitis or pneumonia.2 The FDA based its approval on data from 2 key phase 3 trials in which clesrovimab demonstrated clinically meaningful reductions in RSV-associated disease severity and hospitalizations, Merck said. In the Phase 2b/3 CLEVER trial (N = 3,614), clesrovimab reduced the incidence of RSV-associated medically attended lower respiratory infections (MALRI) by 60.5% compared to placebo (incidence: 0.026 vs 0.065; 95% CI, 44.2-72.0; P <.001) and RSV-associated hospitalizations by 84.3% (incidence: 0.004 vs 0.024; 95% CI, 66.7- 92.6; P <.001). Efficacy increased with disease severity.1

The CLEVER trial investigators enrolled preterm and full-term infants up to age 1 year one year old and showed that a single dose of clesrovimab provided protection throughout the RSV season. The safety profile was comparable to placebo, with most adverse reactions being mild or moderate. Injection-site erythema occurred in 3.8% of clesrovimab recipients, swelling in 2.7%, and rash in 2.3%. Serious hypersensitivity reactions, including anaphylaxis, have been observed with similar IgG1 monoclonal antibodies, and clesrovimab is contraindicated in infants with a history of serious hypersensitivity to any of its components, Merck said in the statement.1

Supportive data from the phase 3 SMART trial (N=896) compared clesrovimab to palivizumab in high-risk infants, including those born at less than 29 weeks gestational age or with chronic lung disease or congenital heart disease.2 The incidence of RSV-associated MALRI and hospitalizations was comparable between the 2 agents (MALRI: clesrovimab 3.6%, palivizumab 2.9%; hospitalization: clesrovimab 1.3%, palivizumab 1.5%). Pharmacokinetic analyses supported efficacy extrapolation from the CLEVER trial to this high-risk population. Safety outcomes were consistent with earlier findings.2

Clesrovimab is intended for use from birth for infants born during the RSV season, or prior to the season for those born earlier. A second dose is recommended following cardiopulmonary bypass in infants undergoing cardiac surgery during RSV season. Co-administration with routine pediatric vaccines has not shown any new safety concerns, according to the manufacturer.1

The Centers for Disease Control and Prevention’s Advisory Committee on Immunization Practices is expected to review clesrovimab for recommendation later this month. Merck plans to make clesrovimab available in the U.S. ahead of the 2025–2026 RSV season, with ordering beginning in July.1

References

1. US FDA approves Merck’s ENFLONSIA™ (clesrovimab-cfor) for prevention of respiratory syncytial virus (RSV) lower respiratory tract disease in infants born during or entering their first RSV season. News release. Merck. June 9, 2025. Accessed June 9, 2025. https://www.merck.com/news/u-s-fda-approves-mercks-enflonsia-clesrovimab-cfor-for-prevention-of-respiratory-syncytial-virus-rsv-lower-respiratory-tract-disease-in-infants-born-during-or-entering-their-fir/

2. Merck’s clesrovimab (MK-1654), an investigational respiratory syncytial virus (RSV) preventative monoclonal antibody significantly reduced incidence of RSV disease and hospitalization in healthy preterm and full-term infants. News release. Merck. October 17, 2024. Accessed June 9, 2025. https://www.merck.com/news/mercks-clesrovimab-mk-1654-an-investigational-respiratory-syncytial-virus-rsv-preventative-monoclonal-antibody-significantly-reduced-incidence-of-rsv-disease-and-hospitalization-in-heal/