FDA Accepts sBLA for Clesrovimab-cfor in Second RSV Season

The US Food and Drug Administration (FDA) has accepted a supplemental Biologics License Application (sBLA) for clesrovimab-cfor (Enflonsia), Merck's extended half-life monoclonal antibody, to expand its indication to include prevention of respiratory syncytial virus (RSV) lower respiratory tract disease (LRTD) in children under 2 years of age at increased risk for severe RSV through their second RSV season, according to the company.¹

The FDA has set a Prescription Drug User Fee Act (PDUFA) target action date of March 22, 2027, for the expanded indication.¹ Clesrovimab-cfor is currently approved only for infants born during or entering their first RSV season, delivered as a single, non-weight-based 105 mg dose.¹ The European Medicines Agency (EMA) accepted a parallel application for the same expanded 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, MPH, vice president and therapeutic area head of global clinical development at Merck Research Laboratories.¹ “The recent FDA and EMA regulatory filings represent important opportunities to help expand protection with ENFLONSIA for vulnerable children under 2 years of age during their second RSV season, potentially further reducing the significant burden of RSV on families and health care systems.”

How Was Clesrovimab-cfor Studied For Second-Season Dosing?

Both applications draw on the phase 3 SMART trial (MK-1654-007; NCT04938830), a randomized, partially-blind, palivizumab-controlled study evaluating the safety, efficacy, and pharmacokinetics of clesrovimab-cfor in infants and children at increased risk for severe RSV disease across 2 RSV seasons.¹ The trial enrolled early preterm infants (younger than 29 weeks gestational age), moderate preterm infants (29 to 35 weeks gestational age), and infants with chronic lung disease (CLD) of prematurity or congenital heart disease (CHD) of any gestational age.¹

In season 1, participants were randomized 1:1 to a single 105 mg intramuscular dose of clesrovimab-cfor (n = 502) or monthly intramuscular palivizumab (n = 501).¹ Eligible participants, defined as children under 2 years of age with CLD, CHD, or early or moderate preterm birth with certain risk conditions, received an additional open-label 210 mg dose of clesrovimab-cfor in season 2 (n = 276), including 138 who received clesrovimab-cfor and 138 who received palivizumab in season 1.¹ Nearly all season 2 recipients, 99%, had CLD (n = 229) or CHD (n = 43).¹

What is Safety Profile of Clesrovimab-cfor?

In the published SMART trial results, RSV-associated medically attended lower respiratory infection through day 180 after the season 2 dose occurred in 7.3% of recipients (95% CI, 4.4%-11.4%), compared with a season 1 incidence of 3.2% (95% CI, 1.8%-5.2%) for clesrovimab-cfor and 3.4% (95% CI, 2.0%-5.6%) for palivizumab through day 150.² The study authors concluded clesrovimab-cfor was well tolerated across both seasons, supporting its use in children who remain at risk for severe RSV disease into a second season.²

Per its current US label, the most common adverse reactions associated with clesrovimab-cfor are injection-site erythema (3.8%), injection-site swelling (2.7%), and rash (2.3%).¹ Serious hypersensitivity reactions, including anaphylaxis, have been observed with other human IgG1 monoclonal antibodies, and clesrovimab-cfor is contraindicated in infants with a history of serious hypersensitivity to any component of the product.¹ The FDA originally approved clesrovimab-cfor in June 2025, followed by European Commission approval in April 2026, and the agent is now approved in more than 40 countries for use in infants during their first RSV season.¹

Clesrovimab-cfor is Merck's only RSV preventive option administered at a fixed dose regardless of weight, designed to provide direct, rapid, and durable protection through 5 months.¹ Regulatory filings for the expanded second-season indication are underway in additional countries beyond the US and EU, alongside continued filings for first-season approval where the agent is not yet authorized.¹

References

1. Merck. 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. 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. Zar HJ, et al. 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