Because clinical trials are conducted under widely varying conditions, adverse reaction rates observed in the clinical trials of a drug cannot be directly compared to rates in the clinical trials of another drug and may not reflect the rates observed in practice.

A total of 3,224 pediatric subjects received the recommended dose of BEYFORTUS in Phase 2 and Phase 3 clinical trials (Trials 03, 04, and 05) including 2,119 infants who were born at 35 weeks gestational age (GA) or older, and 1,105 infants who were born at less than 35 weeks GA. A total of 247 infants of any GA with chronic lung disease (CLD) of prematurity or hemodynamically significant congenital heart disease (CHD) in Trial 05 received the recommended dose of BEYFORTUS.

Neonates and Infants Entering Their First RSV Season (Trial 03 and Trial 04)

Trial 03 was a randomized, double-blind placebo-controlled trial conducted in preterm infants born at a GA of greater than or equal to 29 weeks to less than 35 weeks. Subjects were randomized 2:1 to receive BEYFORTUS (N=968) or placebo (N=479) by IM injection. All subjects randomized to BEYFORTUS received a single 50 mg IM dose regardless of body weight. Safety data in Trial 03 are presented only for the infants in the BEYFORTUS arm who received the recommended dose [infants who weighed less than 5 kg and who received a single dose of 50 mg BEYFORTUS IM (N=572) or placebo (N=288)].

Trial 04 was a Phase 3, randomized, double-blind, placebo-controlled trial conducted in late preterm and term infants born at greater than or equal to 35 weeks GA. Trial 04 enrolled subjects sequentially into two cohorts: the Primary Cohort was used for the primary efficacy analysis [see Clinical Studies (14.3)] and for assessment of safety, and the Safety Cohort was used primarily for safety assessment. All subjects from both cohorts of Trial 04 were included in the safety analysis (BEYFORTUS N=1,997 and placebo N=997). Subjects in Trial 04 weighing less than 5 kg received a single 50 mg IM dose of BEYFORTUS and infants weighing greater than or equal to 5 kg received a single 100 mg IM dose. 

Infants who received the recommended dose in Trial 03 and infants in Trial 04 were pooled to evaluate the safety of BEYFORTUS (N=2,570) compared to placebo (N=1,284). At randomization, in this pooled Safety Population from Trials 03 and 04 cohorts, 22% of infants were born at less than 35 weeks GA, 10% of infants were GA greater than or equal to 35 weeks and less than 37 weeks; 68% were GA greater than or equal to 37 weeks; 52% were male; 57% were White; 15% were Black; 4% were American Indian/Alaskan native; 4% were Asian; 1% were Pacific Islander; and 19% were Other or Mixed Race; 30% were Hispanic or Latino; 73% were from Northern Hemisphere; and 53% weighed less than 5 kg. The median age was 2 months; 65% were less than or equal to 3 months; 28% were greater than 3 to less than or equal to 6 months, and 7% were greater than 6 months of age. (Refer to Sections 14.2 and 14.3, Clinical Studies, for a description of the efficacy populations in Trials 03 and 04). In both trials, infants received a single dose of IM BEYFORTUS or placebo on Study Day 1 and were monitored for at least 60 minutes post-dose. Subjects were followed for 360 days post-dose to assess safety. Adverse reactions were reported in 1.2% of subjects who received BEYFORTUS; most (97%) of adverse reactions were mild to moderate in intensity.

Table 3 summarizes the adverse reactions that occurred in Trial 03 and Trial 04 (Safety Population) in subjects who received the recommended dose of BEYFORTUS.

Infants Born at <35 Weeks Gestational Age and Infants and Children with CLD of Prematurity or Hemodynamically Significant CHD (Trial 05)

RSV Season One

The safety of BEYFORTUS was evaluated in Trial 05, a randomized, double-blind, palivizumab-controlled multicenter trial in infants at high risk for severe RSV disease. These subjects were randomized 2:1 to receive BEYFORTUS (N=614) or palivizumab (N=304) by IM injection. The 614 infants who received BEYFORTUS included 128 preterm infants born at GA less than 29 weeks, 390 preterm infants who were born at 29 weeks or older to less than 35 weeks GA, and 96 late preterm and term infants born at 35 weeks GA or older. Among infants enrolled during their first RSV season, the number of infants with CLD of prematurity or hemodynamically significant CHD were overall 214 and 103, respectively, regardless of gestational age. Of these, 12 infants had both CLD and CHD. 

Subjects in Trial 05 weighing less than 5 kg received a single 50 mg IM dose of BEYFORTUS and infants weighing greater than or equal to 5 kg received a single 100 mg IM dose. BEYFORTUS was administered once on Study Day 1 followed by 4 monthly IM doses of placebo; palivizumab was administered IM monthly for 5 months. All subjects were monitored for at least 60 minutes post-dose. Subjects were followed for 360 days post-dose to assess safety. 

Adverse reactions reported among Trial 05 subjects who received BEYFORTUS in their first RSV season were similar to those reported in subjects who received BEYFORTUS in Trials 03 and 04.

RSV Season Two (Subjects with CLD of Prematurity and Hemodynamically Significant CHD)

Subjects with CLD of prematurity or hemodynamically significant CHD could continue in Trial 05 and receive BEYFORTUS or palivizumab prior to their second RSV season. All subjects who received BEYFORTUS in the first RSV season also received BEYFORTUS in the second RSV season (N=180). Subjects who received palivizumab in the first RSV season were re-randomized to receive BEYFORTUS (N=40) or palivizumab (N=42) in the second RSV season. Safety data were available for 150 days after dosing in children with CLD or CHD who received BEYFORTUS (N=220) or palivizumab (N=42) in their second RSV season. The safety profile of BEYFORTUS in these children during their second RSV season was consistent with the safety profile of BEYFORTUS observed during their first RSV season.