Merck’s Clesrovimab (Enflonsia) Receives FDA Approval to Protect Infants from RSV During First Season
Enflonsia, a single-dose, long-acting antibody, has been FDA-approved to significantly reduce RSV infections and hospitalizations in infants, providing new hope for protecting vulnerable babies during RSV season.
The US Food and Drug Administration (FDA) has approved Merck’s clesrovimab (MK-1654), a long-acting monoclonal antibody designed to provide passive immunization against respiratory syncytial virus (RSV) for infants during their first RSV season. This single-dose, weight-independent treatment demonstrated strong efficacy in pivotal Phase 2b/3 trials,reducing medically attended RSV lower respiratory infections by 60.5% and RSV-related hospitalizations by 84.3% compared to placebo. Merck plans to make clesrovimab available for the 2025-26 RSV season, expanding preventative options beyond currently approved therapies.1
“We’re very proud that the FDA has approved clesrovimab, which is now called enflonsia, for the prevention of RSV for newborns entering their first RSV season,” said Macaya Douoguih, MD, MPH, therapeutic area head for global vaccine clinical development at Merck. “We do plan to make enflonsia available for ordering in July with shipments that will be delivered before the start of the upcoming season later this fall.”
RSV remains a leading cause of hospitalization and death in infants worldwide, highlighting the critical need for effective prevention. Enflonsia’s approval positions Merck alongside Sanofi and AstraZeneca’s Beyfortus, the first FDA-approved long-acting RSV antibody, which has shown 90% effectiveness against RSV hospitalizations.
“Monoclonal antibodies have a very important role to play in terms of addressing the significant burden of RSV, which still remains the leading cause of hospitalization in infants in the US today,” Douoguih added. “It also affirms that demonstrating safety and efficacy through rigorous randomized placebo or active control trials is essential for approval.”
FDA Accepts Merck’s Biologics License Application for Infant RSV Protection
On December 17, 2024, the FDA accepted Merck’s Biologics License Application (BLA) for enflonsia (MK-1654), a long-acting monoclonal antibody designed to protect infants from RSV during their first RSV season.2
The BLA was supported by data from the Phase 2b/3 CLEVER trial, a randomized placebo-controlled study evaluating a single dose of enflonsia in healthy preterm and full-term infants (birth to 1 year). The trial demonstrated a 60.5% reduction in medically attended RSV lower respiratory infections (MALRI) and an 84.3% reduction in RSV-related hospitalizations through Day 150, regardless of infant weight. Interim data from the ongoing Phase 3 SMART trial, comparing enflonsia to palivizumab in infants at increased risk for severe RSV disease, further support the safety and efficacy of enflonsia.2
“The approval was based on results from our Phase 2b/3 trial called CLEVER, which evaluated a single dose of enflonsia administered to preterm and full-term infants from birth up to age one, and the trial met its key primary and secondary endpoints,” said Douoguih. “We showed an efficacy of 60.5%, and importantly, we also demonstrated protection against hospitalization—84.3%. Hospitalization is one of the most important outcomes that worry not only clinicians but also the parents.”
Merck’s Long-Acting RSV Antibody Shows High Efficacy in Infant Prevention Studies
In an October 2024 interview at IDWeek, Anushua Sinha, MD, infectious disease physician and product development lead at Merck, presented results from the Phase 2b/3 CLEVER trial, which enrolled 3,614 healthy preterm and full-term infants. The double-blind, placebo-controlled study showed enflonsia reduced medically attended lower respiratory infections by 60.5%, RSV-related hospitalizations by 84.3%, and hospitalizations due to RSV-associated lower respiratory infections by 90.9% over 150 days. Additionally, severe cases of MALRI declined by 91.7%. Safety data indicated a comparable profile to placebo, with no treatment-related deaths.3,4,5
“What our data show is that we see increasing efficacy with increasing disease severity—and that’s a very important finding,” Douoguih noted. “Our monoclonal combines the convenience of dosing with the strong clinical data showing significant reductions in RSV disease and hospitalizations. It’s really a new, promising preventive option for our large US population.”
Interim findings from the ongoing Phase 3 SMART trial, which compares enflonsia with the current standard of care, palivizumab, in high-risk infants, including those with chronic lung or congenital heart disease, showed comparable safety and efficacy, supporting clesrovimab’s use across both healthy and high-risk infant populations.
“Our approval is also supported by the results from another trial that we did, a Phase 3 trial called SMART, where we evaluated the safety and effectiveness of enflonsia versus palivizumab,” Douoguih explained. “Those two trials were pivotal in supporting the approval.”
