Merck's RSV antibody meets goals in infant study

Merck & Co. has announced promising results for its investigational monoclonal antibody, clesrovimab (MK-1654), in a Phase IIb/III clinical trial aimed at preventing respiratory syncytial virus (RSV) in newborns. The study successfully met all primary safety and efficacy endpoints, which may set the stage for competition with Sanofi and AstraZeneca's Beyfortus (nirsevimab).

RSV is a significant cause of hospitalization in healthy infants worldwide. Paula Annunziato, senior vice president of infectious diseases and vaccines at Merck Research Laboratories, emphasized the potential impact of these findings, expressing optimism about working with regulatory authorities to offer a new preventive option for RSV in infants.

The MK-1654-004 trial assessed clesrovimab in 3,632 healthy preterm and full-term infants, who were randomly administered a single intramuscular dose of either clesrovimab or a placebo. The primary efficacy endpoint was the incidence of RSV-associated medically attended lower respiratory infections (MALRI) from day 1 to 150 post-dose, compared to the placebo group. Detailed findings from the study will be presented at an upcoming scientific forum.

Beyfortus, developed by Sanofi and AstraZeneca, received European approval in 2022 and FDA approval the following year. It is intended to protect newborns and infants, particularly those entering their first RSV season, from lower respiratory tract disease caused by RSV. In the US, Beyfortus is also approved for children up to two years old who remain at risk for severe RSV disease during their second RSV season. Priced at $495 per dose, Beyfortus has been recommended by a panel from the US Centers for Disease Control and Prevention for infant protection against RSV.

Analysts from Jefferies suggest that Merck's clesrovimab may face challenges in competing with Beyfortus. They argue that Beyfortus has already set a high efficacy benchmark and has gained significant traction with real-world data and rapid clinical adoption. For clesrovimab to pose a competitive threat, it would need to show a significantly greater reduction in RSV lower respiratory tract infections (LRTI). Preliminary trials indicate that clesrovimab’s primary endpoint might align with Beyfortus, suggesting only a minimal impact on Beyfortus' anticipated peak sales of €3.75 billion ($4.1 billion).

A Phase I/IIa study involving 64 infants showed that a 100-mg dose of clesrovimab reduced the risk of infection by 80.6% compared to a placebo over 150 days. Using model-based analysis, Jefferies estimates that a single 100-mg dose could provide approximately 77.5% protection against LRTIs over the same period. To be considered a formidable competitor to Beyfortus, Merck's candidate would need to demonstrate an 80%-90% reduction in RSV-associated LRTI hospitalizations or at least 90% to significantly challenge Beyfortus, especially given its recent impressive real-world data published in The Lancet.

Beyond Beyfortus, other RSV preventive measures include Pfizer's RSV vaccine Abrysvo, approved for maternal use to protect infants, and GSK's Arexvy, which currently leads the market. Moderna's mRESVIA, another newcomer, also targets older adults. These developments highlight the competitive landscape in RSV prevention, particularly as it pertains to vulnerable populations like infants and older adults.