Nirsevimab

The European Commission has approved Enflonsia (clesrovimab) for the prevention of RSV lower respiratory tract disease in neonates and infants during their first RSV season. Merck noted that the product is the first RSV preventive option in the European Union not requiring weight-based dosing. The authorization covers all 27 EU member states as well as Iceland, Liechtenstein, and Norway, and adds to prior approvals in the US, Canada, and Switzerland. The EC authorization permits a fixed 105 mg intramuscular dose regardless of infant weight, designed to provide protection across five months — the duration of a typical RSV season. For infants born during the RSV season, the label specifies administration within the first week of life; for those born outside the season, dosing should occur shortly before it begins. Infants undergoing cardiac surgery with cardiopulmonary bypass are recommended an additional 105 mg dose once stable post-surgery. The product carries a contraindication for infants with hypersensitivity to clesrovimab or its excipients, and Merck said the timing of country-level availability will depend on completion of reimbursement procedures. The approval is supported by data from two trials. The pivotal Phase IIb/III CLEVER trial (NCT04767373) enrolled 3,614 preterm and full-term infants randomized 2:1 to a single 105 mg dose of clesrovimab or saline placebo. The primary endpoint — incidence of RSV-associated medically attended lower respiratory infection through 150 days — was reduced by 60.4% versus placebo (95% CI: 44.1, 71.9; p<0.001). RSV-associated hospitalization through five months, the key secondary endpoint, was reduced by 84.2% (95% CI: 66.6, 92.6; p<0.001). Exploratory analyses showed a 91.7% reduction in severe medically attended lower respiratory infection and a 90.9% reduction in RSV-associated lower respiratory tract hospitalization over the same period. The safety profile was comparable to placebo, with the most frequent adverse reactions being injection-site pain (6.5%), injection-site erythema (4.4%), injection-site swelling (3.2%), and rash (2.3%), the majority mild or moderate. Supporting data came from an interim analysis of the Phase III SMART trial (NCT04938830), which compared clesrovimab against monthly palivizumab in 896 infants at increased risk for severe RSV disease. Incidence rates of medically attended lower respiratory infection and hospitalization were comparable between the two arms, with efficacy in the high-risk population established by pharmacokinetic extrapolation from the CLEVER trial. Results from both studies were published in the New England Journal of Medicine in September 2025. The RSV market context RSV is among the leading causes of infant hospitalization globally, capable of progressing to bronchiolitis and pneumonia in both healthy and high-risk infants. Until recently, prophylaxis options were limited largely to palivizumab (Synagis; AstraZeneca), a monthly weight-based injection restricted in most health systems to high-risk populations due to cost and dosing burden. The 2023 approval of nirsevimab (Beyfortus; AstraZeneca/Sanofi) broadened access to a single-season, single-dose option for all infants, and clesrovimab now joins that class with a fixed-dose presentation that Merck said eliminates the need for weight-based calculation at the point of care. The clesrovimab EC approval adds to a growing field of long-acting monoclonal antibodies for infant RSV prophylaxis, with the fixed-dose feature representing a practical distinction from palivizumab and a potential implementation consideration for healthcare systems evaluating uptake. The CLEVER and SMART data also indicate that the antibody maintains activity in high-risk subgroups — including preterm infants and those with chronic lung disease or congenital heart disease — populations where the historical standard of care had been palivizumab administered monthly across the season. The broader RSV prevention and treatment landscape continues to evolve. Pfizer’s maternal RSV vaccine Abrysvo received FDA approval for maternal immunization in 2023, offering an alternative route to infant protection via transplacental antibody transfer, and Moderna’s mRNA-1345 maternal immunization program remains in Phase III investigation. Both approaches, if widely adopted, could affect demand for prophylactic monoclonal antibodies across the infant population. On the treatment side, no antiviral is approved for RSV in infants; investigational agents including ziresovir (Ark Biosciences) and sisunatovir (Pfizer) are in Phase II/III and Phase II evaluation respectively for RSV lower respiratory tract infection treatment in hospitalized infants, a niche that prophylactic antibodies do not address. Merck itself is pursuing MK-5348, an RSV polymerase inhibitor, in Phase I/II for treatment indications, positioning the company across both the preventive and potential therapeutic segments of the RSV space. Leave a Reply Cancel reply Your email address will not be published. Required fields are marked * Comment * Name * Email * Website