The safety and PK of BEYFORTUS were evaluated in a Phase 2/3 randomized, double-blind, palivizumab-controlled multicenter trial (Trial 05) in pediatric subjects born less than 35 weeks GA and infants with CLD of prematurity or hemodynamically significant CHD. This trial was not powered for efficacy, but efficacy was assessed as secondary endpoint. The efficacy of BEYFORTUS in preterm infants (GA less than 35 weeks) during their first RSV season and in pediatric subjects up to 24 months of age with CLD or CHD during their first and second RSV season was established by extrapolation of efficacy of BEYFORTUS from Trials 03 and Trial 04 to the population enrolled in Trial 05 based on similar nirsevimab-alip exposures among subjects enrolled in Trial 04 and 05 [see Clinical Pharmacology (12.3)].

Trial 05: RSV Season One

Trial 05 enrolled infants at higher risk for severe RSV disease entering their first RSV season into one of two cohorts: preterm infants (GA less than 35 weeks) and infants with CLD of prematurity or hemodynamically significant CHD. A total of 925 infants were randomized 2:1 in each of the preterm (n=615) and CLD/CHD (n=310) cohorts to receive BEYFORTUS or palivizumab. Infants received a single IM dose of BEYFORTUS (50 mg if less than 5 kg body weight or 100 mg if greater than 5 kg body weight at the time of dosing), followed by 4 once-monthly IM doses of placebo, or 5 once-monthly IM doses of 15 mg/kg palivizumab, respectively. At randomization, in the preterm cohort, 77 infants (13%) were less than 29 weeks GA; and 499 (81%) were GA greater than or equal to 29 to less than 35 weeks. In the CLD/CHD cohort, 70% had CLD of prematurity; 34% had hemodynamically significant CHD; 123 infants (40%) were less than 29 weeks GA, 28% were greater than or equal to 29 weeks to less than 35 weeks GA; and 32% were greater than or equal to 35 weeks GA. In both cohorts together, 54% were male; 79% were White; 10% were Black; 5% were Asian; 2% were American Indian/Alaskan Native; 15% were Hispanic or Latino; and 57% weighed less than 5 kg. The median age was 3.5 months (range: 0.07 to 12.3 months); 45% were less than or equal to 3 months; 34% were greater than 3 months to less than or equal to 6 months, and 21% were greater than 6 months of age.

In the first RSV season of Trial 05, the incidence of MA RSV LRTI through 150 days post dose was 0.6% (4/616) in the BEYFORTUS group and 1.0% (3/309) in the palivizumab group.

Trial 05: RSV Season Two

Pediatric subjects with CLD of prematurity or hemodynamically significant CHD up to 24 months of age continued in the trial for a second RSV season (n=262). Subjects who received BEYFORTUS during their first RSV season also received a single dose of 200 mg BEYFORTUS entering their second RSV season followed by 4 once-monthly IM doses of placebo (n=180). Subjects who received palivizumab during their first RSV season were re-randomized 1:1 to either receive BEYFORTUS or palivizumab entering their second RSV season. Forty subjects who received palivizumab in the first RSV season received a single IM dose of BEYFORTUS followed by 4 once-monthly IM doses of placebo in their second RSV season; and 42 subjects received palivizumab (5 once-monthly IM doses of 15 mg/kg palivizumab) in both first and second RSV seasons.

In the second RSV season of Trial 05, there were no cases of MA RSV LRTI through Day 150 post-dose in subjects who received either BEYFORTUS or palivizumab.