Nirsevimab

The Smart study looked at infants and young children at increased risk for severe respiratory syncytial virus (RSV)—due to prematurity, chronic lung disease of prematurity or hemodynamically significant congenital heart disease—over two RSV seasons. As Enflonsia approaches the one-year anniversary of its approval, Merck is padding the case for a label expansion that could see the protective antibody better match Sanofi and AstraZeneca’s rival infant respiratory syncytial virus (RSV) preventive Beyfortus. In new results from the late-stage Smart trial—which helped win Enflonsia its initial green light based on interim data last June—Merck’s immunizing antibody appeared safe in kids under 2 years old who remained at risk for severe RSV through their second RSV season and who received Enflonsia at the start of that second season, Merck said in a Feb. 19 release. Specifically, the antibody’s safety profile was “generally consistent” with that observed in infant trial participants who received Enflonsia during their first RSV season, Merck explained. Moreover, Merck’s preventive helped children in the study achieve monoclonal antibody serum concentrations that were “similar to those in healthy infants” who participated in a separate phase 2b/3 study dubbed Clever. The new Smart results “support extrapolation of efficacy” in the population observed in the trial, Merck said in the release.The Smart study specifically looked at infants and young children at increased risk for severe RSV—due to prematurity, chronic lung disease of prematurity or hemodynamically significant congenital heart disease—over two RSV seasons. Merck says it plans to share the results—which were presented at a meeting of the Respiratory Syncytial Virus Foundation in Rome this week—with the FDA and other regulators in hopes of winning an expanded indication in children at higher risk of severe RSV through their second season.  As it stands, Enflonsia’s label only covers (PDF) the antibody’s use in newborns and infants entering their first RSV season, while AZ and Sanofi’s increasingly entrenched Beyfortus is cleared (PDF) by the FDA for the first season as well as in children up to 2 years old who remain vulnerable to severe RSV through their second season. Merck’s Enflonsia won its U.S. green light last summer, teeing up a launch into the current RSV season, which typically begins in November and runs through April. Merck did not break out sales of Enflonsia separately when it reported its full-year 2025 performance earlier this month. The New Jersey drugmaker is no doubt hoping to capture some of the same momentum that has defined Beyfortus’ first few years on the market.After winning an initial U.S. nod in July 2023, Beyfortus has gone on to do gangbusters for Sanofi and AZ, growing total sales 9.5% last year for a total haul of 1.78 billion euros (roughly $2.1 billion) in 2025. Still, clouds may be gathering on the horizon for infant RSV shots Enflonsia and Beyfortus, at least in the U.S.  In December, the FDA notified Merck, AstraZeneca and Sanofi of a safety investigation into their RSV products, with a Merck spokesperson at the time noting that it welcomed the FDA’s questions and that the “evidentiary bar for establishing the safety of vaccines and preventive mAbs like Enflonsia is exceptionally, and appropriately, high.” Though not traditional vaccines, Enflonsia and Beyfortus seem to have been nevertheless caught up in the U.S.’ safety review of many other approved prophylactics under Robert F. Kennedy Jr.’s Department of Health and Human Services.