FDA approves clesrovimab to protect infants during first RSV season

On June 9, 2025, the FDA approved Merck's monoclonal antibody clesrovimab (Enflonsia) to protect infants from respiratory syncytial virus (RSV) disease during their first RSV season, according to a press release from Merck.^1,2

The biologics license application, accepted by the FDA on December 17, 2024, and subsequent approval from the federal agency were based on results from the phase 2b/3 CLEVER trial (MK-1654-004; NCT04767373), a randomized placebo-controlled trial evaluating a single dose of clesrovimab administered to healthy preterm and full-term infants. In addition, data from the phase 3 SMART trial (MK-1654-007) evaluating the safety and efficacy of clesrovimab vs palivizumab in infants and children at an increased risk for severe RSV disease was used in the application submission.²

"RSV disease is the leading cause of infant hospitalization in the US and can lead to serious respiratory conditions like bronchiolitis and pneumonia," said Octavio Ramilo, MD, chair, Department of Infectious Diseases, St. Jude Children's Research Hospital, Memphis, Tennessee, in a press release. "[Clesrovimab] combines dosing convenience with strong clinical data showing significant reductions in RSV disease incidence and hospitalizations, making it a promising new intervention to help protect infants from RSV.”¹

Data from the phase 2b/3 study, announced at IDWeek 2024, revealed that clesrovimab demonstrated positive outcomes, meeting all prespecified endpoints that evaluated a single dose in healthy preterm and full-term infants aged birth to 1 year. Results were consistent through both the 5-month and 6-month time points. The study enrolled 3,632 participants who were randomized 2:1 to receive either a single fixed dose of clesrovimab (105 mg intramuscular injection (IM) or placebo on day 1.³

A reduction in incidence of RSV-associated medically attended lower respiratory infections (MALRI) that required 1 or more indicator of lower respiratory infection or severity compared to placebo through 5 months post-dose, was 60.5% (95% CI: 44.2, 72.0, [P <0.001]).¹

A key secondary endpoint was RSV-associated hospitalizations, for which clesrovimab reduced these hospitalizations by 84.3% (95% CI: 66.7, 92.6, [P <0.001]) through 5 months compared to placebo. A third endpoint was RSV-associated lower respiratory infection hospitalizations, which were reduced 90.9% with clesrovimab treatment compared to placebo through 5 months (95% CI: 76.2, 96.5). In addition, clesrovimab reduced the incidence of severe MALRI (tertiary endpoint) by 91.7% (95% CI: 62.9, 98.1).

"Clesrovimab is a very interesting monoclonal antibody," Ramilo previously told Contemporary Pediatrics. "It has been shown in vitro to neutralize more than 96% of all RSV A and RSV B strains. It targets a different site. Other monoclonals, the one that is on the market, which is nirsevimab, targets a site called site zero. [Clesrovimab] is a bit different because it targets site four in the RSV protein F. This is important because this site four is present in both conformations, in the pre-fusion and post-fusion."

The extended half-life monoclonal antibody is administered using non-weight-based dosing and is designed to provide direct, rapid, and durable protection through 5 months, a typical RSV season. For those born during the RSV season, clesrovimab should be administered starting from birth.

"[Clesrovimab] provides an important new preventive option to help protect healthy and at-risk infants born during or entering their first RSV season with the same dose regardless of weight,” said Dean Y. Li, MD, PhD, president, Merck Research Laboratories. “We are committed to ensuring availability of ENFLONSIA in the U.S. before the start of the upcoming RSV season to help reduce the significant burden of this widespread seasonal infection on families and health care systems.”

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. Merck. Press release. 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. Fitch J. FDA accepts BLA for clesrovimab to prevent RSV in infants' first RSV season. Contemporary Pediatrics. December 17, 2024. Accessed June 2, 2025. https://www.contemporarypediatrics.com/view/fda-accepts-bla-for-clesrovimab-to-prevent-rsv-in-infants-first-rsv-season

3. Fitch J. Clesrovimab: A potential new player to protect against RSV. Contemporary Pediatrics. October 18, 2024. Accessed June 2, 2025. https://www.contemporarypediatrics.com/view/clesrovimab-a-potential-new-player-to-protect-against-rsv