This report summarizes pivotal trials underpinning the FDA approval of Enflonsia™ (clesrovimab‑cfor), an extended‑half‑life monoclonal antibody targeting the RSV fusion glycoprotein, for prophylaxis of RSV lower respiratory tract disease in neonates and infants entering their first RSV season.
In the phase 2b/3 CLEVER trial (NCT04767373), 3,614 healthy preterm and full‑term infants (born ≥29 weeks’ gestation) were randomized 2:1 to a single 105‑mg intramuscular dose of clesrovimab (n = 2,411) or saline placebo (n = 1,203). Through 150 days post‑dosing, clesrovimab reduced medically attended lower respiratory infections by 60.5% (incidence: 2.6% vs. 6.5%; 95% CI, 44.2–72.0; P < .001) and RSV‑associated hospitalizations by 84.3% (0.4% vs. 2.4%; 95% CI, 66.7–92.6; P < .001).
In the phase 3 SMART trial (NCT04938830), 896 high‑risk infants and children were randomized to clesrovimab 105 mg IM on day 1 with placebo on day 28 (n = 446) or monthly palivizumab (n = 450). RSV‑associated lower respiratory infections occurred in 3.6% (95% CI, 2.0–6.0) versus 2.9% (95% CI, 1.5–5.2), and hospitalization rates were comparable (1.3% vs. 1.5%). Adverse events were primarily mild injection‑site reactions.
Therefore, Enflonsia offers a weight‑independent, single‑dose preventive option; however, long‑term effectiveness and real‑world safety warrant further surveillance.
