A single-dose RSV antibody held up against five monthly shots in high-risk babies
The SMART trial tested clesrovimab against palivizumab in premature and heart- and lung-affected infants. It was built to show safety, not to prove one prevents more RSV than the other.
Clesrovimab, a long-acting antibody given as one shot to protect babies through their first respiratory syncytial virus (RSV) season, was as well tolerated as the older antibody palivizumab in infants at high risk of severe disease — premature babies and those with chronic lung or heart conditions — in a phase 3 trial that also followed them into a second season [s1]. The key point for readers is what the trial was and was not: it was designed to establish safety and to describe RSV outcomes, not to prove that one dose of clesrovimab prevents more RSV than five monthly doses of palivizumab [s1].
RSV is the leading cause of infant hospitalisation for lung infection worldwide. Two approaches now exist to shield newborns: vaccinate the mother in pregnancy so protective antibodies cross the placenta, or give the baby a ready-made antibody directly. Clesrovimab (sold as Enflonsia) is one of the direct antibodies, cleared by the US Food and Drug Administration in June 2025 for babies born during or entering their first RSV season [s2]. Most of the pivotal data for these newer antibodies came from otherwise healthy or late-preterm infants; the high-risk babies who most need protection were largely studied separately, which is what this trial set out to fill.
What the trial did
The SMART trial was a randomised, partially masked, phase 3 study at 110 sites in 27 countries, enrolling infants eligible for palivizumab — those with prematurity, chronic lung disease of prematurity, or hemodynamically significant congenital heart disease — between November 2021 and November 2025 [s1]. In the first RSV season, 997 infants were randomly assigned 1:1: one group received a single dose of clesrovimab (105 mg) followed by a placebo injection four weeks later, and the other received monthly palivizumab (15 mg/kg) for up to five doses [s1]. Eligible children who remained at risk were then offered an open-label 210 mg dose of clesrovimab before their second RSV season, and 276 received it [s1]. The comparator matters: palivizumab is the established option for exactly this high-risk group, but it requires an injection every month through the season, so a single-shot alternative would be a practical advance if it holds up.
The trial's design ranked its questions deliberately. The primary outcome was simply the proportion of infants who had adverse events after each antibody in season one — a safety comparison [s1]. How much RSV disease occurred was a secondary, descriptive objective, not a powered head-to-head test of efficacy [s1].
What it found
The 997 infants had a median age of 2.6 months, and half were boys [s1]. In season one, the proportions experiencing adverse events were comparable between the clesrovimab (498 infants) and palivizumab (499 infants) groups, and the 210 mg dose was well tolerated in season two [s1]. On the descriptive disease measures, RSV-associated medically attended lower respiratory infection through day 150 of season one occurred in 3.2% of clesrovimab recipients (95% confidence interval 1.8 to 5.2) and 3.4% of palivizumab recipients (95% confidence interval 2.0 to 5.6) — closely overlapping [s1]. After the season-two dose, total RSV-associated medically attended lower respiratory infection through day 180 was 7.3% (95% confidence interval 4.4 to 11.4) [s1].
How to read it
The result supports using clesrovimab in high-risk infants and, into a second season, in children who remain vulnerable — a group that older trials of the newer antibodies had not directly addressed [s1]. The practical draw is dosing: one injection versus up to five over a season. But the evidence has a clear ceiling. Because the trial was powered for safety and used palivizumab as an active comparator rather than placebo, the near-identical RSV rates cannot be read as proof that clesrovimab is as effective as palivizumab; they are reassuring, descriptive, and confidence-interval-wide [s1]. The study was funded by the antibody's maker, and the season-two disease figure comes from an open-label arm with no comparison group [s1].
Clesrovimab sits alongside a fast-moving field of RSV prevention. The maternal-vaccine route is covered in the effectiveness data from a large Argentine rollout and in the WHO's clearance of a multi-dose maternal vaccine vial, while 25 years of infant RSV mortality data from Kilifi, Kenya is a reminder of what is at stake where none of these products yet reach.
What to watch
The open questions are real-world effectiveness against hospitalisation in high-risk infants, how clesrovimab and the alternative antibody nirsevimab compare, and whether a second-season dose earns a place in immunisation schedules [s1]. This article describes research and a regulatory decision and is not medical advice.
Sources
- Clesrovimab in Infants at Increased Risk For Severe Disease During 2 RSV Seasons — JAMA Pediatrics, 20 July 2026
- Drugs@FDA: Enflonsia (clesrovimab-cfor), BLA 761432 — US Food and Drug Administration, approved 9 June 2025
Sources
- Clesrovimab in Infants at Increased Risk For Severe Disease During 2 RSV Seasons: A Randomized Clinical Trial — JAMA Pediatrics , July 20, 2026
- Drugs@FDA: Enflonsia (clesrovimab-cfor), BLA 761432 — US Food and Drug Administration , June 9, 2025
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