Phase 3 SMART Trial Supports Clesrovimab for High-Risk Children in Second RSV Season

Merck announced positive second-season findings from the phase 3 SMART clinical trial (MK-1654-007; NCT04938830) evaluating clesrovimab (ENFLONSIA™), an extended half-life monoclonal antibody, in infants and children aged younger than 2 years who remain at increased risk for severe respiratory syncytial virus (RSV) disease through a second RSV season. The data were presented at RSVVW’26 and will be shared with the US Food and Drug Administration (FDA) and other regulatory authorities to support a potential expanded indication.

“All children who received ENFLONSIA in their second RSV season were at increased risk for severe RSV disease, and nearly all had chronic lung disease or congenital heart disease,” Dr. Paolo Manzoni, Head of Maternal–Infant Medicine, University of Torino Hospital Degli Infermi, Ponderano, Italy, and an investigator for the SMART clinical trial, said in a press release. “These new findings from SMART demonstrate the potential of ENFLONSIA to help protect these vulnerable children, who may require an additional dose for their second RSV season.”

In children entering a second RSV season who received a 210-mg dose of clesrovimab (administered as two 105-mg intramuscular injections), safety was generally consistent with that observed in infants who received clesrovimab during their first RSV season. No drug-related serious adverse events (SAEs) were reported. Solicited adverse events during days 1 through 5 postdose included irritability (13.0%), somnolence (8.7%), decreased appetite (6.9%), injection-site pain (4.3%), injection-site erythema (1.8%), injection-site swelling (1.8%), and fever (1.1%).

Serum concentrations of clesrovimab achieved in children younger than 2 years at increased risk during their second RSV season were similar to those observed in healthy infants in the pivotal phase 2b/3 CLEVER trial (MK-1654-004; NCT04767373), supporting extrapolation of efficacy to this population. Among children who received clesrovimab in RSV season 2, incidence rates of RSV-associated medically attended lower respiratory infection (MALRI) with at least 1 indicator of lower respiratory infection or severity and RSV-associated hospitalization were 7.3% (95% CI, 4.4-11.4) and 3.0% (95% CI, 1.3-5.9), respectively, through day 180 (6 months). Investigators noted that these rates reflect the children’s higher baseline risk and post–COVID-19 RSV disease burden.

The SMART trial was a randomized, partially blinded, palivizumab-controlled, multicenter study enrolling early (<29 weeks gestational age) and moderate preterm infants (≥29 to ≤35 weeks gestational age) as well as infants with chronic lung disease (CLD) of prematurity or congenital heart disease (CHD). In RSV season 1, 502 participants received a single 105-mg dose of clesrovimab and 501 received monthly palivizumab. In RSV season 2, 276 eligible children younger than 2 years with CLD, CHD, or certain prematurity-related risk conditions received open-label clesrovimab; 99% had CLD (n=229) or CHD (n=43).

Season 1 data demonstrated that the safety profile of clesrovimab was similar to palivizumab. Incidence rates of RSV-associated MALRI through day 150 (5 months) were 3.2% (95% CI, 1.8-5.2) in the clesrovimab group and 3.4% (95% CI, 2.0-5.6) in the palivizumab group. RSV-associated hospitalization occurred in 1.0% (95% CI, 0.3-2.4) and 1.7% (95% CI, 0.7-3.3), respectively. No drug-related SAEs were reported.

Clesrovimab is currently approved in the US, Canada, and several other countries for passive immunization to prevent RSV lower respiratory tract disease in newborns and infants entering their first RSV season. In the United States, the approved dose is 105 mg (0.7 mL) administered intramuscularly, regardless of infant weight, and designed to provide protection for approximately 5 months.

RSV remains a leading cause of hospitalization among infants globally, with children younger than 2 years who have prematurity, CLD, or CHD at particularly high risk for severe disease. The second-season SMART data will be submitted to regulators to evaluate a potential expanded indication for children at increased risk entering a second RSV season.

Reference: 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. News item. Merck. February 19, 2026. Accessed February 19, 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/