Clesrovimab Given in 1st and 2nd RSV Seasons for At-Risk Infants

After a comparative trial confirmed a single, long-acting dose of clesrovimab provides similar protection to monthly palivizumab injections for neonates and infants at risk of serious respiratory synctial virus (RSV) disease in their first season, an open label extension demonstrated clesrovimab effective and well-tolerated when repeated in their 2nd season.¹

Heather Zar, MD, PhD, Department of Pediatrics & Child Health, Univeristy of Cape Town, Cape Town South Africa, and colleagues explain that while clesrovimab is approved for the prevention of RSV lower respiratory tract disease in neonates and infants born during or entering their first RSV season, "data concerning clesrovimab from a second RSV season among children who remain at risk for severe disease are needed."

They point out that all infants are at risk for RSV disease in the first 6 months of life, but those born preterm and with comorbidities such as chronic lung disease of prematurity or congenital heart disease remain at increased risk in their second year of life.

The investigators enrolled and randomized 1,003 infants for their first RSV season; of whom 997 were dosed, with 498 receiving a single 105mg injection of clesrovimab and 499 receiving up to 5 monthly injections of palivizumab 15mg/kg. Most in the palivizumab group received 3 monthly doses, but could receive up to two additional doses depending on their enrollment date relative to the RSV season, and consistent with local standard of care.

The primary outcomes were safety, including proportion of participants experiencing solicited (injection site and systemic) adverse events.Secondary outcomes included the incidence of RSV-associated medically attended lower respiratory infection. To identify cases of RSV-associated disease, the investigators conducted weekly active surveillance 180 days after the first dose of active treatment. At completion of the first season comparative trial, the proportion of participants in both groups experiencing adverse events and the incidence rates of RSV-associated disease were similar.

In the open-label extension, 271 participants with continued risk of severe RSV disease received clesrovimab 210mg up to 4 weeks before the second RSV season. The total incidence rates of RSV-associated disease and of related hospitalization through day 180 after the 210 mg dose were 7.3% (95% CI 4.4-11.4%) and 3.0% (1.3-5.9%), respectively, which were comparable to that in the first season.The investigators note that these comparable results were found despite most participants (approximately 98%) in the second season open extension were followed during post-COVID-19 pandemic seasons 2023 to 2025, which had higher rates of RSV disease compared with pre-pandemic seasons.

An exploratory pharmacokinetics measure found that serum concentrations were similar with the 105mg dose for infants in season 1, and the 210mg in their second season.The investigators suggested that this further justified that 210mg is an appropriate dose for children who remain at risk in their second RSV season.

"A 210 mg dose of clesrovimab was generally well-tolerated in children who remained at increased risk for severe disease in their second year of life," conclude Zar and colleagues."The safety profile of a 210mg second season dose of clesrovimab was comparable between children receiving clesrovimab over 2 consecutive RSV seasons and who had received palivizumab in their first RSV season."

Reference

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;180(9):951–960. doi:10.1001/jamapediatrics.2026.2760.