FDA Accepts Merck's BLA for Clesrovimab, an Investigational mAb Against RSV in Infants

Merck announced today that the FDA has accepted the company’s Biologics License Application for clesrovimab (MK-1654), an investigational prophylactic long-acting monoclonal antibody (mAb) for infants to protect them from respiratory syncytial virus (RSV) disease during their first RSV season.

The FDA has set a Prescription Drug User Fee Act (PDUFA) date of June 10, 2025, which means clesrovimab would be available for ordering in July, with shipments arriving in time for the 2025 RSV season, the company said in the announcement.

The passive immunization, an extended half-life mAb, if approved, would be administered as a single, weight-neutral shot, according to Merck. In clinical trials clesrovimab is being studied in healthy preterm, full-term, and at-risk infants to provide direct and durable protection against mild, moderate, and severe RSV during their first vulnerable respiratory virus season.

“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,” Paula Annunziato, MD, senior vice president, infectious diseases and vaccines, Global Clinical Development, Merck Research Laboratories, said in the press release.  

Positive data from the pivotal phase 2b/3 CLEVER clinical trial (MK-1654-004) and interim results from the ongoing phase 3 SMART trial (MK-1654-007) support the Merck BLA. The former is a randomized placebo-controlled trial evaluating a single dose of clesrovimab when given to healthy preterm and full-term infants (birth to age 1 year). The study enrolled 3632 infants and met the primary efficacy endpoint specified as reduction in incidence of RSV-associated medically attended lower respiratory infections (MALRI) requiring at least 1 indicator of lower respiratory infection (LRI) or severity vs placebo through 5 months post-dose, which was 60.4% (95% CI: 44.1, 71.9, p<0.001). "CLEVER also met secondary and tertiary endpoints including reduction of RSV-associated hospital admissions by 84% and reduced hospitalization for RSV-associated LRI by more than 90%, according to an October news release."

The phase 3 SMART trial is investigating the safety and efficacy of clesrovimab vs palivizumab in infants and children at risk for severe infection with RSV. Merck announced data from a planned interim analysis at IDWeek in October that showed comparable safety profiles for clesrovimab and palivizumab and no drug-related serious AEs to date. The 2 mAbs were also comparable on Incidence rates of RSV-associated MALRI requiring 1 or more indicators of LRI or severity and RSV-associated hospitalizations at 3.6% and 1.3%, respectively, for clesrovimab and 3.0% and 1.5%, respectively, for pavlizumab through day 150.

“These clinically meaningful findings also reinforce the potential for clesrovimab to be the first and only immunization designed to protect both healthy and at-risk infants using the same dose, regardless of weight,” Annunziato said in October. “We look forward to continuing to discuss these data with health authorities around the world with the goal of making clesrovimab available for infants as early as the 2025-26 RSV season.”

References

1. Merck Announces FDA Acceptance of Biologics License Application for Clesrovimab, an Investigational Long-Acting Monoclonal Antibody Designed to Protect Infants from RSV Disease During their First RSV Season. News release. Merck. December 17, 2024. Accessed December 17, 2024. https://www.merck.com/news/merck-announces-fda-acceptance-of-biologics-license-application-for-clesrovimab-an-investigational-long-acting-monoclonal-antibody-designed-to-protect-infants-from-rsv-disease-during-their-first-rsv/

2. Merck’s Clesrovimab (MK-1654), an Investigational Respiratory Syncytial Virus (RSV) Preventative Monoclonal Antibody, Significantly Reduced Incidence of RSV Disease and Hospitalization in Healthy Preterm and Full-term Infants. News release. Merck. October 17, 2024. Accessed December 17, 2024. https://www.merck.com/news/mercks-clesrovimab-mk-1654-an-investigational-respiratory-syncytial-virus-rsv-preventative-monoclonal-antibody-significantly-reduced-incidence-of-rsv-disease-and-hospitalization-in-heal/