FDA Approves Clesrovimab RSV Immunization for Newborns and Infants

The FDA has approved clesrovimab, under the name Enflonsia, for preventing respiratory syncytial virus (RSV) lower respiratory tract disease in neonates and infants who are born during or entering their first RSV season.1

“RSV disease is the leading cause of infant hospitalization in the U.S. and can lead to serious respiratory conditions like bronchiolitis and pneumonia,” investigator Octavio Ramilo, MD, chair of the Department of Infectious Diseases at St. Jude Children’s Research Hospital, said in a statement.1 “ENFLONSIA 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.”

Clesrovimab is a preventive, long-acting monoclonal antibody (mAb) designed to provide direct, rapid and durable protection through 5 months, covering a typical RSV season. Notably, it is the first and only RSV preventive option administered to infants using the same dose 105 mg regardless of weight.

The FDA approval was based off of data from the pivotal Phase 2b/3 CLEVER trial (MK-1654-004) evaluating a single dose of clesrovimab administered to preterm and full-term infants (from birth to 1 year of age), as well as the Phase 3 SMART trial (MK-1654-007) evaluating the safety and efficacy of ENFLONSIA versus palivizumab in infants at increased risk for severe RSV disease.2

In CLEVER, the trial met its primary end point, with investigators observing that clesrovimab reduced the incidence of RSV-associated medically attended lower respiratory infections (MALRI) requiring ≥1 indicator of lower respiratory infection (LRI) or severity compared to placebo through 5 months by 60.5% (95% CI, 44.2-72.0; P <.001). Specifically, the clesrovimab group had an incidence rate of 0.026 and the placebo group had an incidence rate of 0.065.

Further positive data were seen in secondary end points, with the clesrovimab cohort demonstrating an 84.3% (95% CI, 66.7-92.6; P <.001) reduction in RSV-associated hospitalizations through 5 months (clesrovimab incidence, .004; placebo incidence, .024). Investigators also observed increasing efficacy with increasing disease severity.

“ENFLONSIA 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,” Dean Y. Li, president, MD, PhD, Merck Research Laboratories, added.1 “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.”

REFERENCE

1. U.S. 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. 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. 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/