FDA Approves Clesrovimab to Prevent RSV in Infants During First Season

The FDA has approved clesrovimab-cfor (Enflonsia), Merck’s long-acting monoclonal antibody, for the prevention of respiratory syncytial virus (RSV) lower respiratory tract disease in neonates and infants born during or entering their first RSV season, the company announced.¹

According to Merck, this approval offers providers a second passive immunization option for infants following the 2023 approval of nirsevimab (Beyfortus).² The company expects ordering to begin in July 2025, with shipments to be available before the start of the 2025-2026 RSV season.¹ Clesrovimab-cfor is currently the only RSV preventive approved at a fixed 105-mg dose regardless of infant weight, which may simplify administration, and provides protection for 5 months—the length of a typical RSV season.

RSV is the leading cause of infant hospitalization in the US | Image credit: BHM – stock.adobe.com

The approval was based on results from the pivotal phase 2b/3 CLEVER trial (NCT04767373), which enrolled 3614 infants born preterm and full-term to receive either clesrovimab or placebo.³ Over a 5-month follow-up period, researchers found the monoclonal antibody reduced the incidence of RSV-associated medically attended lower respiratory infections (MALRI) by 60.5% and hospitalizations by 84.3%. The most common adverse events included mild injection-site reactions and rash, with no treatment-related deaths reported.

“RSV disease is the leading cause of infant hospitalization in the U.S. and can lead to serious respiratory conditions like bronchiolitis and pneumonia,” Octavio Ramilo, MD, chair of the department of infectious diseases at St. Jude Children’s Research Hospital and investigator for both the CLEVER and SMART (NCT04938830) trials, 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.”

The SMART trial enrolled high-risk infants, including those born extremely preterm or with chronic lung or congenital heart disease, and compared clesrovimab against palivizumab.⁴ Rates of RSV-related disease and hospitalization were similar between the 2 groups, and clesrovimab’s safety profile was consistent with findings in the CLEVER trial. Merck said efficacy in the SMART trial was supported by extrapolating pharmacokinetic data from CLEVER.¹

Clesrovimab-cfor is administered as a single intramuscular injection. For infants undergoing cardiac surgery with cardiopulmonary bypass, an additional dose is recommended postoperatively. The product is not indicated for infants with a history of serious hypersensitivity reactions to any component.

The CDC’s Advisory Committee on Immunization Practices (ACIP) was expected to meet later in June to issue recommendations for use. However, on June 9, 2025, HHS Secretary Robert F. Kennedy Jr removed all members from ACIP, claiming the independent panel that advises the CDC on vaccine use had been “plagued with persistent conflicts of interest and has become little more than a rubber stamp for any vaccine.”⁵ While there is still no official plan on who he would appoint to the panel, Kennedy said ACIP will convene in the next 2 weeks.⁶

In an October 2024 presentation at IDWeek, Merck reported that clesrovimab reduced hospitalizations due to RSV-associated lower respiratory tract infections by more than 90% and that severe cases of MALRI declined by over 91%.⁷ The company noted that clesrovimab may complement ongoing prevention efforts and ease strain on health systems during RSV season.

References

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. Merck. News release. June 9, 2025. Accessed June 10, 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. Bonavitacola J. FDA approves beyfortus for use in infants with RSV. AJMC^®. July 17, 2023. Accessed June 10, 2025. https://www.ajmc.com/view/fda-approves-beyfortus-for-use-in-infants-with-rsv
3. Efficacy and Safety of Clesrovimab (MK-1654) in Infants (MK-1654-004) (CLEVER). https://clinicaltrials.gov/study/NCT04767373. Updated May 6, 2025. Accessed June 10, 2025.
4. Clesrovimab (MK-1654) in Infants and Children at Increased Risk for Severe Respiratory Syncytial Virus (RSV) Disease (MK-1654-007) (SMART). https://clinicaltrials.gov/study/NCT04938830. Updated May 21, 2025. Accessed June 10, 2025.
5. Grossi G. RFK Jr sweeps clean CDC vaccine advisory panel, aiming to bolster public confidence. AJMC. June 9, 2025. Accessed June 10, 2025. https://www.ajmc.com/view/rfk-jr-sweeps-clean-cdc-vaccine-advisory-panel-aiming-to-bolster-public-confidence
6. Ungar L, Seitz A. RFK Jr. ousts entire CDC vaccine advisory committee. The Associated Press. June 9, 2025. Accessed June 10, 2025. https://apnews.com/article/kennedy-cdc-acip-vaccines-3790c89f45b6314c5c7b686db0e3a8f9
7. 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. Merck. News release. October 17, 2024. Accessed June 10, 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/