FDA Approves Merck’s ENFLONSIA™ to Protect Infants from Severe RSV Illness
Merck operating as MSD outside the United States and Canada, has received a significant regulatory milestone with the U.S. Food and Drug Administration (FDA) granting approval for ENFLONSIA™ (clesrovimab-cfor). This new monoclonal antibody therapy is designed to prevent lower respiratory tract disease caused by respiratory syncytial virus (RSV) in neonates and infants born during or entering their first RSV season. The approval marks an important step in addressing one of the most common and potentially dangerous viral infections affecting infants worldwide.
ENFLONSIA is a long-acting, preventive monoclonal antibody developed specifically to offer sustained protection for up to five months, which typically spans the entire RSV season — from the early fall through late spring. Unlike some treatments that require dosing adjustments based on weight, ENFLONSIA simplifies administration by offering a single fixed 105 mg dose for all infants, regardless of their size. This uniform dosing approach can potentially streamline distribution and administration, making it easier for healthcare providers to implement across diverse clinical settings.
The Urgent Need for RSV Prevention in Infants
Respiratory syncytial virus is the leading cause of infant hospitalizations in the United States, and it is known to trigger severe respiratory illnesses such as bronchiolitis and pneumonia in young children. While the majority of RSV infections result in mild symptoms, certain infants—particularly those born prematurely or with underlying medical conditions—are at higher risk of developing life-threatening complications.
Dr. Octavio Ramilo, Chair of the Department of Infectious Diseases at St. Jude Children’s Research Hospital and lead investigator of the CLEVER (MK-1654-004) and SMART (MK-1654-007) clinical trials, emphasized the significance of this development. “RSV disease is the leading cause of infant hospitalization in the U.S. and can lead to serious respiratory conditions like bronchiolitis and pneumonia,” Dr. Ramilo stated. “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.”
Backed by Strong Clinical Evidence
The FDA’s approval was primarily based on robust data from the pivotal Phase 2b/3 CLEVER trial, which evaluated the safety and efficacy of ENFLONSIA in both preterm and full-term infants up to one year of age. In this randomized, placebo-controlled study, a single dose of ENFLONSIA delivered statistically significant reductions in the incidence of medically attended RSV lower respiratory tract infections.
Key results from the CLEVER trial include:
- A 60.5% reduction in RSV-associated medically attended lower respiratory infections (MALRI) requiring at least one clinical indicator of LRI severity compared to placebo through 5 months. The incidence rate was 0.026 in the ENFLONSIA group versus 0.065 in the placebo group (95% CI: 44.2%, 72.0%, p<0.001).
- An 84.3% reduction in RSV-associated hospitalizations over the same 5-month period compared to placebo. The incidence rate was 0.004 in the ENFLONSIA group versus 0.024 in the placebo group (95% CI: 66.7%, 92.6%, p<0.001), highlighting the therapy’s increasing efficacy with more severe cases.
In addition to the CLEVER trial, the approval was supported by data from the Phase 3 SMART trial, which compared ENFLONSIA to palivizumab, the current standard monoclonal antibody used primarily for high-risk infants. While palivizumab requires monthly injections throughout the RSV season, ENFLONSIA provides a significant advance by offering durable protection with a single dose.
Safety Profile and Precautions
Like all biologic therapies, ENFLONSIA comes with safety considerations. It should not be administered to infants with known serious hypersensitivity reactions, including anaphylaxis, to any of its components. Merck has emphasized the importance of adhering to these precautions and consulting the full prescribing information to ensure appropriate patient selection.
The most common adverse events observed during clinical trials were generally mild to moderate in nature and consistent with those seen in other antibody-based prophylactic therapies. Additional safety data are expected to be collected as ENFLONSIA is introduced into broader clinical use.
A New Era in Infant RSV Protection
Dr. Dean Y. Li, President of Merck Research Laboratories, underscored the importance of this approval for the company’s pediatric infectious disease portfolio. “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,” Dr. Li stated. “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.”
Indeed, Merck’s approach to RSV prophylaxis with ENFLONSIA reflects the evolving landscape of pediatric infectious disease prevention. The company aims not only to offer a scientifically sound intervention but also to ensure broad and equitable access to the product. ENFLONSIA is expected to be especially beneficial in community settings where monthly injections may not be feasible due to resource limitations or inconsistent access to pediatric care.
Next Steps: CDC Advisory and Commercial Availability
The next crucial milestone in the rollout of ENFLONSIA will come from the U.S. Centers for Disease Control and Prevention (CDC). The agency’s Advisory Committee on Immunization Practices (ACIP) is scheduled to meet later in June to review the clinical data and provide usage recommendations for ENFLONSIA. These guidelines will be essential in shaping how the therapy is adopted within public and private pediatric care programs.
Merck has indicated that ordering of ENFLONSIA is expected to begin in July, with commercial shipments scheduled for delivery ahead of the 2025-2026 RSV season. This timeline positions the company to make a strong impact during the upcoming fall and winter months when RSV cases typically surge across the U.S.
Broader Implications and Outlook
ENFLONSIA joins a growing class of next-generation RSV prophylactic treatments aiming to reduce the global burden of respiratory diseases in vulnerable pediatric populations. With RSV accounting for millions of hospital visits worldwide annually and causing a substantial economic and emotional toll on families, preventive strategies like ENFLONSIA represent an important advancement in child health.
The simplified dosing, long duration of protection, and compelling clinical results position ENFLONSIA as a competitive new option in a market where innovation has been limited for years. It also reflects Merck’s continued investment in pediatric medicine, infectious disease research, and public health infrastructure.
As more data becomes available and international regulatory submissions proceed, Merck is expected to explore further label expansions, including use in high-risk children beyond their first RSV season and potentially even in older pediatric populations with chronic health conditions. Moreover, real-world evidence collected in the first seasons of ENFLONSIA’s deployment will likely help refine clinical practice guidelines and further validate its utility across diverse demographic settings.
In summary, the FDA’s approval of ENFLONSIA marks a pivotal moment in the fight against RSV in infants. By offering a powerful, easy-to-administer, and long-lasting solution to prevent a major cause of infant hospitalization, Merck is helping to close a critical gap in pediatric respiratory care.
