Clesrovimab shows promise in high-risk infants across 2 RSV seasons

Clesrovimab (Enflonsia; Merck & Co) has displayed positive safety and efficacy results in infants and children with an increased risk of severe respiratory syncytial virus (RSV) disease across 2 RSV seasons, according to Merck.¹

The phase 3 SMART trial (MK-1654-007; NCT04938830) included children aged under 2 years. When receiving clesrovimab at the start of their second RSV season, infants presented with similar safety results vs those observed in the CLEVER trial (MK-1654-007; NCT04767373), when the drug was administered during RSV season 1.

“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,” said Paolo Manzoni, MD, PhD, head of maternal–infant medicine at the University of Torino Hospital Degli Infermi.

Comparing clesrovimab and palivizumab

Participants in the SMART trial included early or moderate preterm infants presenting with chronic lung disease (CLD) of prematurity or congenital heart disease (CHD). Significant improvements in monoclonal antibody serum concentrations were also observed in these patients.

Participants were randomly assigned 1:1 to either a 105-mg clesrovimab dose group or a monthly intramuscular (IM) palivizumab group. An additional open-label, 210-mg dose of clesrovimab was provided through 2 IM injections of 105 mg to eligible patients in the second RSV season.

CLD or CHD was present in 99% of patients receiving clesrovimab in RSV season 2. The drug showed a similar safety profile to palivizumab, with no drug-related serious adverse events reported.

Positive safety and efficacy findings

Adverse events in the clesrovimab group included irritability in 28.8%, somnolence in 18.9%, decreased appetite in 13.5%, injection site pain in 7.8%, injection site erythema in 6.2%, injection site swelling in 6.2%, and fever in 0.8%. In the palivizumab group, these rates were 33.7%, 22%, 13.2%, 10.8%, 6.4%, 5.6%, and 1.2%, respectively.

Comparable rates of RSV-associated, medically attended lower respiratory infection were also reported between treatment modalities. Coughing or difficulty breathing was reported in 3.2% of the clesrovimab group through day 150 and RSV-associated hospitalization in 1%. In the palivizumab group, these rates were 3.4% and 1.7%, respectively.

Season 2 findings indicated similar rates of adverse events. Additionally, RSV-associated medically attended lower respiratory infection through day 180 was reported in 7.3% of patients receiving clesrovimab and RSV-associated hospitalization in 3%.

Implications and FDA approval

According to investigators, these data highlight increased baseline risk in these children, alongside an increase in RSV disease burden after the COVID-19 pandemic. As an extended half-life monoclonal antibody, clesrovimab allows for passive immunization that can prevent RSV lower respiratory tract disease in newborns and infants.

“These new data from the SMART study further position Enflonsia as an important potential new option to help protect young children who remain at high risk entering their second RSV season,” said Macaya Douoguih, MD, MPH, vice president of Merck Research Laboratories.

Clesrovimab was approved for RSV prevention in young infants by the FDA in June 2025.² This approval was based on results from the CLEVER trial, where the medication displayed a reduction in lower respiratory infections and RSV-associated hospitalizations. These results highlight the protective effect of clesrovimab.

References

1. 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 release. Merck.February 19, 2026. Accessed February 19, 2026. https://www.businesswire.com/news/home/20260219213035/en/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
2. 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. News release. Merck. June 9, 2025. Accessed February 19, 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/