FDA Approves Clesrovimab to Prevent RSV in Infants

The FDA has approved clesrovimab, marketed as Enflonsia, for the prevention of RSV lower respiratory tract disease in neonates and infants during their first RSV season.

ENFLONSIA is a preventive, long-acting monoclonal antibody (mAb) designed to provide direct, rapid and durable protection through 5 months, a typical RSV season, with the same 105 mg dose regardless of weight. A typical RSV season usually spans autumn to spring of the next year.

“RSV disease is the leading cause of infant hospitalization in the U.S. and can lead to serious respiratory conditions like bronchiolitis and pneumonia,” said Dr. Octavio Ramilo, chair of the Department of Infectious Diseases at St. Jude Children’s Research Hospital and investigator for the CLEVER (MK-1654-004) and SMART (MK-1654-007) trials. “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.”

ENFLONSIA should not be administered to infants with a history of serious hypersensitivity reactions, including anaphylaxis, to any component of ENFLONSIA. See additional Selected Safety Information below.

The approval is based on results from the pivotal Phase 2b/3 CLEVER trial (MK-1654-004) evaluating a single dose of ENFLONSIA administered to preterm and full-term infants (birth to 1 year of age). The trial met its primary and key secondary endpoints, as outlined below.

• ENFLONSIA demonstrated a reduction in 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 (primary endpoint) by 60.5% (95% CI: 44.2, 72.0, p<0.001) (incidence rates: ENFLONSIA, 0.026; placebo, 0.065).

• ENFLONSIA demonstrated a reduction in RSV-associated hospitalizations through 5 months (key secondary endpoint) by 84.3% (95% CI: 66.7, 92.6, p<0.001) (incidence rates: ENFLONSIA, 0.004; placebo, 0.024), showing increasing efficacy with increasing disease severity.

The approval is also supported by results from 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.

“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 Dr. Dean Y. Li, president, Merck Research Laboratories. “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.”

The U.S. Centers for Disease Control and Prevention’s (CDC’s) Advisory Committee on Immunization Practices is expected to meet later this month to discuss and make recommendations for the use of ENFLONSIA in infants. Ordering is anticipated to begin in July, with shipments delivered before the start of the 2025-2026 RSV season.

About ENFLONSIA™ (clesrovimab-cfor)

ENFLONSIA (clesrovimab-cfor) is Merck’s extended half-life monoclonal antibody (mAb) indicated for passive immunization for the prevention of respiratory syncytial virus (RSV) lower respiratory tract disease in newborns and infants who are born during or entering their first RSV season. ENFLONSIA is administered using non-weight-based dosing and is designed to provide direct, rapid and durable protection through 5 months, a typical RSV season. For infants born during the RSV season, ENFLONSIA is to be administered starting from birth. For infants born outside of the RSV season, ENFLONSIA should be administered prior to the start of their first RSV season. For infants undergoing cardiac surgery with cardiopulmonary bypass during or entering their first RSV season, an additional 105 mg dose is recommended as soon as the infant is stable after surgery.