By IDSE News Staff
The FDA accepted the biologics license application (BLA) for clesrovimab (MK-1654), Merck’s investigational, prophylactic, long-acting monoclonal antibody (mAb) designed to protect infants from respiratory syncytial virus (RSV) disease during their first RSV season.
The agency set a Prescription Drug User Fee Act (PDUFA) date of June 10, 2025.
The application is supported by results from the pivotal phase 2b/3 CLEVER trial (MK-1654-004), a randomized, placebo-controlled trial evaluating a single dose of clesrovimab administered to healthy preterm and full-term infants (age, birth to 12 months), and interim results from the ongoing phase 3 SMART trial (MK-1654-007) evaluating the safety and efficacy of clesrovimab versus palivizumab in infants and children at increased risk for severe RSV disease. Data from these trials were presented during IDWeek in October 2024.
MK-1654-004 evaluated a broad spectrum of RSV disease, ranging from mild outpatient illness to severe disease requiring hospitalization. The primary efficacy end point of the trial, reduction in incidence of RSV-associated medically attended lower respiratory infections (MALRI) requiring at least one indicator of lower respiratory infection (LRI) or severity compared with placebo through day 150 (five months) post-dose, was 60.4% (95% CI, 44.1-71.9; P<0.001). Clesrovimab also reduced RSV-associated hospitalizations (secondary end point) and RSV-associated LRI hospitalizations (tertiary end point) through day 150 (five months) compared with placebo by 84.2% (95% CI, 66.6-92.6; P<0.001) and 90.9% (95% CI, 76.2-96.5), respectively. Clesrovimab reduced the incidence of severe MALRI (tertiary end point) by 91.7% (95% CI, 62.9-98.1).
In addition, in a post hoc analysis, the reduction in incidence of MALRI requiring two or more indicators of LRI and severity (an end point of more severe MALRI than the primary MALRI end point), was 88.0% (95% CI, 76.1-94.0) through day 150 (five months).
The drug study also met its primary end points in the SMART trial.
Clesrovimab is an investigational, extended half-life mAb developed as a passive immunization for the prevention of RSV disease. Clesrovimab is designed to be administered as the same single dose, regardless of body weight, and is being studied in healthy preterm, full-term and at-risk infants to provide direct, rapid and durable protection through their first RSV season against mild, moderate and severe RSV.
“Despite recent advances in RSV prevention, unmet needs remain for additional effective interventions to help protect infants and continue to help address the burden RSV places on families and the healthcare system. This regulatory milestone, along with promising results from our pivotal studies demonstrating efficacy in the prevention of RSV disease, marks important progress toward our goal of having clesrovimab available in time for the 2025-26 RSV season,” said Paula Annunziato, MD, the senior vice president of infectious diseases and vaccines, Global Clinical Development, at Merck Research Laboratories. “We look forward to working alongside the FDA on the review of clesrovimab, which, if approved, would be the first and only single-dose immunization for infants regardless of weight designed to protect them for the duration of their first RSV season.”
RSV is the leading cause of hospitalization for healthy infants younger than 12 months, and a major cause of death in low- and middle-income countries. RSV can lead to serious respiratory conditions like bronchiolitis and pneumonia, causing an estimated 3.6 million hospitalizations and 101,000 deaths a year worldwide in children under age 5.
If approved, Merck anticipates that clesrovimab would be available for ordering by physicians and healthcare administrators by July, with shipments arriving in time for the 2025 RSV season.
