Merck (NYSE: MRK), known as MSD outside the U.S. and Canada, has shared positive results from its Phase 2b/3 clinical trial (MK-1654-004) evaluating clesrovimab, an investigational monoclonal antibody designed to protect infants from respiratory syncytial virus (RSV) during their first RSV season. These findings, along with interim data from an ongoing Phase 3 trial (MK-1654-007), were presented at IDWeek 2024, held October 16-19 in Los Angeles.
The Phase 2b/3 trial evaluated a single dose of clesrovimab in healthy preterm and full-term infants (up to one year old) and met all pre-defined endpoints. Results showed that clesrovimab significantly reduced RSV-associated hospitalizations by 84.2% and RSV-related lower respiratory infection hospitalizations by 90.9% compared to placebo through five months post-dose. Additionally, the reduction in severe medically attended lower respiratory infections (MALRI) was 91.7%. Safety data indicated that adverse events (AEs) and serious AEs were similar between clesrovimab and placebo groups, with no treatment-related or RSV-related deaths reported.
Dr. Octavio Ramilo, chair of the Department of Infectious Diseases at St. Jude’s Children’s Research Hospital and a trial investigator, highlighted the significance of these results. “RSV is a leading cause of hospitalization for infants, and the study showed a broad impact on RSV cases, from mild to severe disease,” he said. “The reduced incidence of RSV-related hospitalizations underscores the potential of clesrovimab to alleviate the burden of RSV on infants and families.”
The primary endpoint—reduction in RSV-associated medically attended lower respiratory infections requiring indicators of severity—showed a 60.4% decrease compared to placebo. A post-hoc analysis found an 88.0% reduction in more severe MALRI cases.
Additionally, Merck presented interim results from the Phase 3 MK-1654-007 trial, comparing clesrovimab to palivizumab in infants at higher risk for severe RSV disease. The data indicated comparable safety profiles and similar rates of RSV-associated MALRI and hospitalizations between the two treatments.
Dr. Paula Annunziato, senior vice president of infectious diseases and vaccines at Merck Research Laboratories, noted that the data highlights clesrovimab’s potential to become the first immunization designed for infants using a single dose regardless of weight. “We are eager to continue discussions with health authorities worldwide to make clesrovimab available for the 2025-26 RSV season,” she said.
Merck aims for clesrovimab to offer a new standard in RSV prevention for both healthy and at-risk infants, addressing a significant global health challenge.
About MK-1654-004
MK-1654-004 (NCT04767373) is a Phase 2b/3 double-blind, randomized, placebo-controlled clinical trial to evaluate the safety and efficacy of clesrovimab in healthy preterm and full-term infants from birth to 1 year of age entering their first RSV season. The study enrolled 3,632 participants who were randomized 2:1 to receive either a single fixed dose of clesrovimab (105 mg intramuscular injection (IM)) or placebo on Day 1. Primary endpoints included the incidence of participants with RSV-associated medically attended lower respiratory infection (MALRI) from Day 1 (postdose) to Day 150 as compared to placebo and safety. The MALRI definition required >1 indicator of LRI or severity. RSV-associated hospitalization through Day 150 and MALRI requiring >1 indicator of LRI or severity to Day 180, were prespecified secondary endpoints. Prespecified tertiary endpoints included acute respiratory infection, RSV-associated lower respiratory infection hospitalizations and incidence of severe MALRI through Day 150. In a post hoc analysis, more severe forms of RSV-associated MALRI (>2 indicators of LRI and severity) were assessed. Across endpoints, additional measures of efficacy were assessed through Day 180. Safety measures included the percentage of participants with solicited injection-related adverse events (AEs), AEs of special interest (AESIs) solicited systemic AEs or serious adverse events (SAEs).
About MK-1654-007
MK-1654-007 (NCT04938830) is a Phase 3, multicenter, randomized, partially blinded, controlled study to evaluate the safety, efficacy, and pharmacokinetics of clesrovimab in infants and children at increased risk for severe RSV disease compared to palivizumab. The study enrolled participants who were entering their first RSV season and recommended to receive palivizumab due to prematurity (≤35 weeks gestational age), chronic lung disease (CLD) of prematurity, or hemodynamically significant congenital heart disease (CHD). Participants were randomized 1:1 to receive clesrovimab (105 mg IM on Day 1, placebo on Day 28) or monthly palivizumab in their first season, and eligible participants received clesrovimab (210 mg IM) in the second RSV season. At this interim analysis, 901 participants were enrolled in the trial. The primary endpoint is safety and tolerability of clesrovimab versus palivizumab in the first season. Secondary endpoints include the incidence of RSV-associated medically attended lower respiratory infections (MALRI) requiring ≥1 indicator of LRI or severity and of RSV-associated hospitalization through Day 150.
About clesrovimab (MK-1654)
Clesrovimab (MK-1654) is an investigational, extended half-life monoclonal antibody (mAb) developed as a passive immunization for the prevention of RSV. Clesrovimab is designed to be administered as the same single dose, regardless of birth 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.
About RSV
Respiratory syncytial virus (RSV) is a contagious virus that causes widespread seasonal infections like the flu, with a worldwide burden in infants and older adults. There is high unmet need for preventative options in both healthy and high-risk infants. Globally, RSV is the leading cause of hospitalization for healthy infants under a year old. RSV can lead to serious respiratory conditions like bronchiolitis and pneumonia, causing an estimated 101,000 deaths a year worldwide in children under five. According to the CDC, RSV season starts in the fall and peaks in the winter in most regions of the United States, but timing and severity in a given community or region can vary year to year.
