Merck's investigational monoclonal antibody, clesrovimab, has demonstrated a significant reduction in respiratory syncytial virus (RSV)-related infections and hospitalizations in infants, according to Phase 2b/3 trial results presented at IDWeek 2024. The MK-1654-004 trial (NCT04767373) showed a favorable safety profile alongside the efficacy data, suggesting its potential as a single-dose preventive treatment for both healthy and at-risk infants.
Efficacy of Clesrovimab in Preventing RSV
The Phase IIb/III double-blind, randomized, placebo-controlled MK-1654-004 trial analyzed the safety and efficacy of clesrovimab in healthy preterm and full-term infants from birth to one year of age entering their first RSV season. The study randomly assigned 3,632 participants in a 2:1 ratio to receive a single fixed dose of clesrovimab 105 mg via intramuscular injection on day one compared with placebo. The trial’s primary endpoints included safety and incidence of RSV-associated medically attended lower respiratory infection (MALRI) from day one to day 150 vs. placebo.
Clesrovimab achieved all of the trial’s prespecified endpoints. The incidence of RSV-associated MALRI requiring at least one indicator of lower respiratory infection (LRI) or severity for clesrovimab vs. placebo through five months postdose was 60.4% (95% CI: 44.1, 71.9, p<0.001).
Dr. Octavio Ramilo, chair of the Department of Infectious Diseases at St. Jude’s Children’s Research Hospital and a trial investigator, highlighted the potential of clesrovimab to alleviate the burden of RSV on infants and their families, noting that the study evaluated a broad spectrum of RSV disease, from mild outpatient illness to severe disease requiring hospitalization.
Reduction in Hospitalizations and Severe Disease
In addition to reducing the overall incidence of RSV-associated MALRI, clesrovimab also significantly lowered the rates of hospitalizations and severe disease. Through five months, clesrovimab reduced RSV-associated hospitalizations by 84.2% (95% CI: 66.6, 92.6, p<0.001) compared to placebo. It also lowered RSV-associated LRI hospitalizations by 90.9% (95% CI: 76.2, 96.5) compared to placebo. Furthermore, the incidence of severe MALRI was reduced by 91.7% (95% CI: 62.9, 98.1).
Safety Profile and Comparison to Palivizumab
The safety profile of clesrovimab was found to be comparable to placebo, with similar rates of adverse events (AEs) and serious AEs in both cohorts. Notably, there were no treatment or RSV-related deaths reported in the trial.
Interim data from the multicenter, randomized, partially blinded, controlled MK-1654-007 trial, which compared clesrovimab to palivizumab in infants and children at elevated risk for severe RSV disease, indicated a comparable safety profile between the two treatments. While incidence rates of RSV-associated MALRI requiring at least one indicator of LRI or severity were slightly higher in the clesrovimab cohort (3.6%) compared to the palivizumab cohort (1.3%), RSV-associated hospitalization rates were similar (3.0% vs. 1.5%, respectively) through five months.
Potential Impact and Future Availability
Dr. Paula Annunziato, senior vice president, infectious diseases and vaccines, Global Clinical Development, Merck Research Laboratories, emphasized the potential of clesrovimab to lessen the significant impact of RSV on infants, families, and healthcare systems. Merck aims to discuss the data with health authorities globally, with the goal of making clesrovimab available for infants as early as the 2025-26 RSV season.
The development of clesrovimab comes at a crucial time, given the shortages of the RSV vaccine Beyfortus (nirsevimab-alip) experienced during the 2023-2024 RSV season. If approved, clesrovimab could provide a valuable additional option for preventing RSV in infants, potentially reducing the burden of this widespread seasonal infection.
