Clesrovimab Shows Consistent Safety in High-Risk Children Across Two RSV Seasons
Phase III SMART trial data show clesrovimab maintained consistent safety and efficacy in high-risk children across two RSV seasons, with no drug-related serious adverse events reported in either season.
Merck & Co has reported new data from its Phase III SMART trial evaluating Enflonsia (clesrovimab) in infants and children under two years at increased risk for severe respiratory syncytial virus (RSV) disease. Presented at the Respiratory Syncytial Virus Foundation conference in Rome, Italy, the findings focus on participants spanning two RSV seasons.
The partially-blind, randomized, multi-center, palivizumab-controlled trial enrolled early (less than 29 weeks gestational age) or 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 the first RSV season, 502 participants received a single 105mg dose of clesrovimab and 501 received monthly palivizumab administered via intramuscular injection.
In the second season, 276 eligible children under two years with CLD, CHD or certain prematurity-related risk conditions received an open-label 210mg dose of clesrovimab as two 105mg injections. Among the children treated in the second season, 99% had CLD (n=229) or CHD (n=43).
The results indicate that safety in children under two years who received clesrovimab at the start of their second RSV season was generally consistent with that observed during the first season. No drug-related serious adverse events were reported in either season. Solicited adverse events during days 1 through 5 postdose in season 2 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%).
In season 1, 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.
Incidence rates of RSV-associated medically attended lower respiratory infection (MALRI) through day 150 (5 months) in season 1 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.
Among children who received clesrovimab in RSV season 2, incidence rates of RSV-associated 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). These rates reflect the children's higher baseline risk and post-COVID-19 RSV disease burden.
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.
The latest results will be submitted to regulatory authorities, including the FDA, for evaluation towards an expanded indication. Clesrovimab presently holds approval in Canada, the US and several other countries for use in infants during 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. The FDA approved clesrovimab for RSV prevention in young infants in June 2025.