The FDA has approved Merck’s Enflonsia (clesrovimab-cfor), a long-acting monoclonal antibody, for the prevention of respiratory syncytial virus (RSV) lower respiratory tract disease in infants born during or entering their first RSV season. According to the company, approval was based on results from the Phase IIb/III CLEVER trial, which showed a notable reduction in RSV-related hospitalizations as well as medically attended lower respiratory infections (MALRI).¹

What Does Enflonsia Approval Mean for RSV Prevention in Infants?

“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, chair, department of infectious diseases, St. Jude Children’s Research Hospital, investigator for the CLEVER (MK-1654-004) and SMART (MK-1654-007) trials, in a press release. “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.”

CLEVER Trial: Study Design and Primary Results

• The randomized, double-blind, placebo-controlled CLEVER trial evaluated the safety and efficacy of Enflonsia in 3,632 early and moderate preterm infants.
• Patients were randomly assigned in a 2:1 ratio to receive either a single 105 mg dose of Enflonsia or saline placebo by intramuscular (IM) injection.
• The primary endpoint of the study was the incidence of patients with RSV-associated MALRI characterized as cough or difficulty breathing and requiring ≥1 indicator of lower respiratory infection or severity from day one to day 150.
• A key secondary endpoint was RSV-associated hospitalization through five months.1,2
• Results showed a 60.5% reduction in MALRI and an 84.3% reduction in RSV-related hospitalizations compared to placebo.
• The most common adverse events (AEs) were injection-site erythema, injection-site swelling, and rash.
• Patients were monitored for serious AEs for up to a year after post-dose. Most serious AEs were mild to moderate in severity.

SMART Trial: Safety, Efficacy, and Comparison to Palivizumab

• Approval was also supported by the randomized, partially blind, palivizumab-controlled, multi-site Phase III SMART trial, which evaluated the safety and efficacy of Enflonsia in 1,003 infants with increased risk for severe RSV disease.
• This included early and moderate preterm infants as well as infants with chronic lung disease of prematurity or congenital heart disease.
• Patients were randomly assigned in a 1:1 ratio to receive either Enflonsia or palivizumab by IM injection.
• Results show that the safety profile of Enflonsia was generally comparable to that of palivizumab and consistent with the safety data observed in the CLEVER trial.
• In patients treated with Enflonsia, the incidence rate of MALRI and hospitalizations through five months were 3.6% and 1.3%, respectively.
• In patients who were treated with palivizumab, the incidence of MALRI and hospitalizations was 2.9% and 1.5%, respectively.^1,3

Global Impact of RSV and Merck’s Commitment

According to the World Health Organization, RSV causes approximately 3.6 million hospitalizations and 100,000 deaths a year in children under five years of age globally. Half of these deaths are in infants under six months of age. Around 97% of all pediatric deaths occur in low- and middle-income countries, mainly due to limited access to care.⁴

“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,” said Dean Y. Li, president, Merck Research Laboratories, in the press release. “We are committed to ensuring availability of Enflonsia in the US 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.”

Merck intends to make Enflonsia available in the United States ahead of the 2025–2026 RSV season, pending Centers for Disease Control and Prevention recommendations.¹

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. 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. Efficacy and Safety of Clesrovimab (MK-1654) in Infants (MK-1654-004) (CLEVER). Clinicaltrials.gov. Accessed June 10, 2025. https://clinicaltrials.gov/study/NCT04767373

3. Clesrovimab (MK-1654) in Infants and Children at Increased Risk for Severe Respiratory Syncytial Virus (RSV) Disease (MK-1654-007) (SMART). Clinicaltrials.gov. Accessed June 10, 2025. https://clinicaltrials.gov/study/NCT04938830?intr=Clesrovimab&rank=3

4. Respiratory syncytial virus (RSV). WHO. Accessed June 10, 2025. https://www.who.int/news-room/fact-sheets/detail/respiratory-syncytial-virus-(rsv)