Octavio Ramilo, MD, reacts to the FDA approval of clesrovimab for RSV prevention

The June 9, 2025, FDA approval of clesrovimab (Enflonsia; Merck) marked another advancement for the prevention of respiratory syncytial virus (RSV) disease in infants, especially during their first RSV season. The decision adds another tool for providers and clinicians, and continues the momentum seen in recent years regarding RSV and FDA-approved preventive measures.

“I think this is very exciting news. RSV was discovered almost 60 years ago, and until the recent couple of years, we had nothing really effective that could achieve RSV prevention in the whole population," said Octavio Ramilo, MD, chair of the Department of Infectious Diseases at St. Jude Children’s Research Hospital.

With the addition of clesrovimab, alongside nirsevimab and Pfizer's maternal RSV vaccine, Ramilo said clinicians now have multiple tools to offer broader protection.

“Now we move to a totally different era,” he said. “We have 2 monoclonal antibodies, nirsevimab and now clesrovimab, as well as a maternal vaccine, that are all indicated to prevent RSV disease during the first season.”

The approval was based on data from the phase 2b/3 CLEVER trial and the phase 3 SMART trial, which together demonstrated that a single intramuscular dose of clesrovimab significantly reduced medically attended RSV-related lower respiratory tract infections and hospitalizations over a 5-month period—the duration of a typical RSV season. Ramilo explained that clesrovimab is can be differentiated from other preventive RSV tools.

“It targets a different site of the molecule, site four,” he said, adding that this site is present in both the pre-fusion and post-fusion conformations of the RSV protein F. “We use one uniform dose across [infants], so you don’t need to adjust for weight, which is very interesting.”

He also emphasized that early protection is essential, given that hospitalization rates are highest in infants aged 1 to 2 months. Passive immunization strategies, such as monoclonal antibodies or maternal immunization, are better suited than traditional vaccines that require time to generate immunity.

“Data suggests that if babies get infected in the first 6 months of life, the likelihood of having more recurrent respiratory infections is much higher,” Ramilo said. “Maybe we can not only prevent the acute events but have a potential long-term benefit in preventing diseases like wheezing or even asthma. We don't know that yet. Those are the studies that we need to do."

Reference:

Fitch J. FDA approves clesrovimab to protect infants during first RSV season. Contemporary Pediatrics. June 9, 2025. Accessed June 10, 2025. https://www.contemporarypediatrics.com/view/fda-approves-clesrovimab-to-protect-infants-during-first-rsv-season