FDA accepts application to expand clesrovimab-cfor use to high-risk children in second RSV season

The FDA has accepted a supplemental biologics license application (sBLA) from Merck seeking to expand the indication for ENFLONSIA (clesrovimab-cfor) to include children under 2 years of age who remain at increased risk for severe respiratory syncytial virus (RSV) disease entering a second RSV season. ¹The agency has set a Prescription Drug User Fee Act (PDUFA) target action date of March 22, 2027, and the European Medicines Agency 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," Macaya Douoguih, MD, MPH, vice president and therapeutic area head of global clinical development at Merck Research Laboratories, said in a statement, adding that the filings could help extend protection to vulnerable children during a second season.

Clesrovimab trial data supporting the second-season application

The filings draw on the phase 3 SMART trial (MK-1654-007; NCT04938830), a randomized, partially masked, palivizumab-controlled study conducted at 110 sites across 27 countries in infants at increased risk for severe RSV disease, including infants born at 35 weeks¹ gestation or earlier and those with chronic lung disease of prematurity or hemodynamically significant congenital heart disease.² In season 1, 998 infants were randomized 1:1 to a single 105-mg dose of clesrovimab or monthly palivizumab; a subset of 276 children who remained high risk went on to receive an open-label 210-mg dose of clesrovimab before their second season, of whom nearly all had chronic lung disease or congenital heart disease.^1,2

Adverse events occurred in a similar share of clesrovimab and palivizumab recipients in season 1 (75.3% vs 79.6%), as did serious adverse events (24.5% vs 27.5%), and safety in season 2 was generally consistent with what was seen after the first dose.² Full trial results were published online in JAMA Pediatrics in July 2026, following an earlier interim readout in the New England Journal of Medicine in September 2025.^2,3

RSV burden and the gap in second-season options

RSV remains one of the leading causes of infant hospitalization worldwide, and certain children who were protected during their first season—including those born very preterm or with chronic lung or congenital heart disease—can remain vulnerable into their second. Since the 2023 introduction of long-acting monoclonal antibodies, the field has shifted away from monthly palivizumab dosing, which the American Academy of Pediatrics discontinued recommending as of the end of 2025.⁴ Under current AAP guidance, only children aged 8 through 19 months who meet high-risk criteria need RSV immunization in a second season, and nirsevimab—not clesrovimab—is the product currently approved for that indication.⁴ Clesrovimab, first approved by the FDA in June 2025, has so far been indicated only for infants born during or entering their first RSV season, using a single, non-weight-based 105-mg dose intended to protect through a roughly 5-month season.¹

Interpreting the data

The SMART findings are reassuring on safety, but the second-season population studied was relatively small (276 children) and enriched for chronic lung and congenital heart disease, so the results speak most directly to that subgroup rather than to preterm infants without those comorbidities.^1,2 Efficacy conclusions for the second-season dose also rely partly on pharmacokinetic comparisons rather than on a randomized, placebo-controlled assessment of clinical RSV outcomes in season 2 alone, a common approach for monoclonal antibodies but one that leaves some uncertainty about real-world protection in this specific population.² Clinicians should note that clesrovimab is not yet approved for second-season use anywhere, and current guidance still directs eligible high-risk children in that age range to nirsevimab.⁴

References

1. Merck & Co, Inc. 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 increased risk for severe RSV for their second season. News release. 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. Zar HJ, Bont LJ, Manzoni P, et al; SMART (MK-1654-007) Study Group. Clesrovimab in infants at increased risk for severe disease during 2 RSV seasons: a randomized clinical trial. JAMA Pediatr. Published online July 20, 2026. doi:10.1001/jamapediatrics.2026.2760

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. American Academy of Pediatrics. Recommendations for the prevention of RSV disease in infants and children: policy statement. Pediatrics. 2025;156(5):e2025073923.