FDA Accepts Merck's Application to Expand Enflonsia into Second RSV Season

FDA has accepted a supplemental biologics license application (sBLA) from Merck to expand the indication for Enflonsia (clesrovimab-cfor) to include children under 2 years of age at increased risk for severe respiratory syncytial virus (RSV) disease through their second RSV season, with a Prescription Drug User Fee Act (PDUFA) action date of March 22, 2027.¹ The European Medicines Agency (EMA) accepted a parallel application for the same population in July 2026.¹

"For some children, the potentially serious impact of RSV does not stop after their first RSV season," said Macaya Douoguih, MD, vice president, therapeutic area head, global clinical development, at Merck Research Laboratories, in a company press release.¹ "The recent FDA and EMA regulatory filings represent important opportunities to help expand protection with Enflonsia for vulnerable children under two years of age during their second RSV season."

Why does protection matter beyond the first RSV season?

Certain infants remain vulnerable to severe RSV disease beyond their first season, including those with chronic lung disease of prematurity, congenital heart disease, or early or moderate preterm birth with certain risk conditions, even after protection during their first RSV season.¹

What clinical data support the applications?

The applications are supported by the phase 3 SMART trial (MK-1654-007, NCT04938830), a randomized, partially blind, palivizumab-controlled study. In RSV season 1, 502 infants received a single 105-mg dose of Enflonsia and 501 received monthly palivizumab; eligible participants who remained at increased risk entering RSV season 2, comprising 276 children, received an additional open-label 210-mg dose of Enflonsia, with nearly all (99%) having chronic lung disease or congenital heart disease.¹

Season 1 pivotal data, on which Enflonsia's original approval was based, showed an 84.3% reduction in RSV-associated hospitalizations through 5 months versus placebo (95% confidence interval, 66.7-92.6; p<.001).^1,2 Interim season 1 results were published in the New England Journal of Medicine in September 2025,³ and full trial results appeared in JAMA Pediatrics in July 2026.⁴ Season 2 safety data, presented at the RSVVW'26 conference in February 2026, were generally consistent with safety observed in season 1.^1,5

What is the current RSV prevention landscape?

RSV is a leading cause of infant hospitalization worldwide, and current US prevention options include maternal RSV vaccination during pregnancy and 2 long-acting monoclonal antibodies, nirsevimab and Enflonsia, administered to infants for their first RSV season.^1,6 Real-world surveillance during the 2024-2025 RSV season, the first full season with monoclonal antibody and maternal vaccine options widely available, found RSV-associated hospitalization rates among infants up to 43% lower than pre-pandemic seasons.⁶

How does Enflonsia work, and where is it approved?

Enflonsia is a long-acting monoclonal antibody administered at a single, non-weight-based dose of 105 mg, designed to provide direct, rapid, and durable protection for approximately 5 months, a typical RSV season. It was first approved by FDA in June 2025 and by the European Commission in April 2026 for infants in their first RSV season and is now approved in more than 40 countries.¹ The most common adverse reactions in prior trials were injection-site erythema (3.8%), injection-site swelling (2.7%), and rash (2.3%).¹

What are the limitations?

FDA acceptance of the sBLA does not guarantee approval of the expanded indication, and the agency's review will conclude by the March 22, 2027, PDUFA action date. EMA's parallel review timeline was not specified in the release.

References

1. Merck. US FDA accepts sBLA for Enflonsia (clesrovimab-cfor) to update its respiratory syncytial virus (RSV) lower respiratory tract disease indication to include children under two years at increased risk. Press release. Published August 6, 2026. Accessed August 6, 2026. https://www.merck.com/news/u-s-fda-accepts-sbla-for-enflonsia-clesrovimab-cfor-to-update-its-respiratory-syncytial-virus-rsv-lower-respiratory-tract-disease-indication-to-include-children-under-two-years-at-increa/
2. Merck. US 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. Press release. Published June 9, 2025. Accessed August 6, 2026. 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/
3. Zar HJ, Bont LJ, Manzoni P, et al; SMART (MK-1654-007) Study Group. Clesrovimab in infants and children at increased risk for severe RSV disease. N Engl J Med. 2025;393(13):1343-1345. doi:10.1056/NEJMc2506107
4. Zar HJ, Bont LJ, Manzoni P, et al. Clesrovimab in infants at increased risk for severe disease during 2 RSV seasons: a randomized clinical trial. JAMA Pediatr. 2026;e262760. doi:10.1001/jamapediatrics.2026.2760
5. Merck. Merck announces positive new data for Enflonsia (clesrovimab) for infants and children under 2 years of age at increased risk for severe respiratory syncytial virus (RSV) disease over two RSV seasons. Press release. Published February 19, 2026. Accessed August 6, 2026. https://www.merck.com/news/merck-announces-positive-new-data-for-enflonsia-clesrovimab-for-infants-and-children-under-2-years-of-age-at-increased-risk-for-severe-respiratory-syncytial-virus-rsv-disease-over-two-rsv/
6. Moulia DL, Link-Gelles R, Chu HY, et al. Use of clesrovimab for prevention of severe respiratory syncytial virus–associated lower respiratory tract infections in infants: recommendations of the advisory committee on immunization practices—United States, 2025. MMWR Morb Mortal Wkly Rep. 2025;74(32:508–514. Accessed August 6, 2026. https://www.cdc.gov/mmwr/volumes/74/wr/mm7432a3.htm