Merck’s ENFLONSIA receives FDA acceptance for label expansion to prevent severe RSV lower respiratory tract disease in high-risk children during a second RSV season.
Written By: Rishabh Sonawane, BPharm
Reviewed By: Pharmacally Editorial Team
Merck has secured U.S. Food and Drug Administration acceptance of a supplemental Biologics License Application for ENFLONSIA™ (clesrovimab-cfor) to expand its use for preventing respiratory syncytial virus (RSV) lower respiratory tract disease (LRTD) in children younger than two years who remain at increased risk for severe RSV disease during their second RSV season. The FDA assigned a Prescription Drug User Fee Act target action date of March 22, 2027.
The regulatory milestone follows the European Medicines Agency’s acceptance of a corresponding marketing authorization variation application in July 2026 for the same patient population, positioning the monoclonal antibody for potential label expansion across major markets.
ENFLONSIA Addresses Persistent RSV Risk Beyond Infancy
ENFLONSIA is an extended half-life monoclonal antibody that provides passive immunization against RSV by delivering immediate protective antibodies rather than stimulating an immune response. It is currently approved in the United States, European Union, Canada, China, Japan, and more than 40 countries for preventing RSV LRTD in infants during their first RSV season.
The therapy received FDA approval in June 2025 and European Commission approval in April 2026 as the first RSV preventive option for infants that uses a single fixed 105 mg dose regardless of body weight, simplifying administration compared with weight-based dosing approaches.
Although many infants receive protection during their first RSV season, children born prematurely or those with chronic lung disease (CLD) or congenital heart disease (CHD) remain vulnerable to severe RSV infection during a second season, creating an unmet clinical need.
Phase 3 SMART Trial Supported Regulatory Expansion
The supplemental application is supported by findings from the Phase 3 SMART trial (MK-1654-007; NCT04938830), a randomized, partially blinded, multicenter study comparing ENFLONSIA with monthly palivizumab in infants and young children at elevated risk for severe RSV disease.
The trial enrolled early preterm infants (<29 weeks gestational age), moderate preterm infants (29–35 weeks gestational age), and infants with CLD of prematurity or congenital heart disease.
During the first RSV season, 1,003 participants were randomized to receive either a single 105 mg intramuscular dose of ENFLONSIA (n=502) or monthly palivizumab injections (n=501).
Eligible children entering a second RSV season received an open-label 210 mg intramuscular dose of ENFLONSIA (n=276), including participants previously treated with either ENFLONSIA or palivizumab. Nearly all children receiving the second-season dose had CLD (229 participants) or CHD (43 participants).
Results from SMART were presented at RSVVW’26, the ninth Respiratory Syncytial Virus Foundation (ReSViNET) conference in February 2026. Interim first-season findings were previously published in the New England Journal of Medicine, while complete study results appeared in JAMA Pediatrics in July 2026.
Merck Highlights Need for Extended RSV Protection
Macaya Douoguih, MD, vice president and therapeutic area head of Global Clinical Development at Merck Research Laboratories, said that severe RSV risk extends beyond infancy for certain vulnerable children.
She noted that the FDA and EMA submissions represent an opportunity to expand protection with ENFLONSIA during the second RSV season, potentially reducing RSV-related hospitalizations and healthcare burden among children with underlying medical conditions.
Established Safety Profile Supports Ongoing Development
ENFLONSIA carries a contraindication for infants with previous serious hypersensitivity reactions, including anaphylaxis, to the product or its components. Serious allergic reactions have been reported with other human IgG1 monoclonal antibodies and require prompt medical management if they occur.
The antibody may interfere with rapid RSV antigen diagnostic tests, and reverse transcriptase polymerase chain reaction (RT-PCR) testing is recommended when clinical suspicion remains high despite negative antigen results.
The most frequently reported adverse events include injection-site erythema (3.8%), injection-site swelling (2.7%), and rash (2.3%).
Regulatory Development
If approved, ENFLONSIA would become available for an additional dose during the second RSV season for children younger than two years with persistent risk factors such as chronic lung disease, congenital heart disease, or qualifying prematurity. The FDA is expected to complete its review by March 22, 2027, while the EMA is evaluating the corresponding application for the European Union. The proposed expansion would broaden protection for one of the pediatric populations most susceptible to severe RSV disease and further strengthen ENFLONSIA’s global role in RSV prevention.
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About the Writer
Rishabha Sonawane, B.Pharm (LinkedIn) is healthcare writer with a strong interest in medical writing, regulatory affairs, clinical research, and AI-driven drug discovery. He has completed specialized training from the NIH and ICMR in clinical pharmacology, clinical research, and scientific writing. Passionate about evidence-based healthcare communication, he focuses on translating complex scientific research into clear, accurate, and engaging medical content.