Becker's Hospital Review

GA. Trial 04 enrolled subjects sequentially into two cohorts: the Primary Cohort was used for the primary efficacy analysis [see Clinical Studies (14.3) in the full prescribing information] 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=1,998 and placebo N=996). 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 2 summarizes the adverse reactions that occurred in Trial 03 and Trial 04 (Safety Population) in subjects who received the recommended dose of BEYFORTUS. Table 2 Adverse Reactions Reported at an Incidence Higher Than Placebo in the Safety Population * (Trials 03 and 04) Adverse Reaction BEYFORTUS N=2,570 % Placebo N=1,284 % Rash † (occurring within 14 days post-dose) 0.9 0.6 Injection site reaction ‡ (occurring within 7 days post-dose) 0.3 0 *The Safety Population includes all subjects who received the recommended dose of BEYFORTUS in Trials 03 and 04: Primary and Safety cohorts from Trial 04; infants who weighed less than 5 kg and who received the recommended dose of BEYFORTUS (single 50 mg IM dose) in Trial 03. †Rash was defined by the following grouped preferred terms: rash, rash macular, rash maculo-papular, rash papular. ‡Injection site reaction was defined by the following grouped preferred terms: injection site reaction, injection site pain, injection site induration, injection site edema, injection site swelling. 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. 7 DRUG INTERACTIONS 7.1 Interference with RT-PCR or Rapid Antigen Detection RSV Diagnostic Assays Nirsevimab-alip does not interfere with reverse transcriptase polymerase chain reaction (RT-PCR) or rapid antigen detection RSV diagnostic assays that employ commercially available antibodies targeting antigenic site I, II, or IV on the RSV fusion (F) protein. For immunological assay results which are negative when clinical observations are consistent with RSV infection, it is recommended to confirm using an RT-PCR-based assay. 8 USE IN SPECIFIC POPULATIONS 8.1 Pregnancy BEYFORTUS is not indicated for use in females of reproductive potential. 8.2 Lactation BEYFORTUS is not indicated for use in females of reproductive potential. 8.4 Pediatric Use The safety and effectiveness of BEYFORTUS have been established for the prevention of RSV lower respiratory tract disease in neonates and infants born during or entering their first RSV season and in children up to 24 months of age who remain vulnerable to severe RSV disease through their second RSV season. The safety and efficacy of BEYFORTUS for this indication and populations are discussed throughout the labeling. Use of BEYFORTUS for this indication is supported by evidence from adequate and well-controlled studies in neonates and infants from birth up to 12 months of age with additional pharmacokinetic and safety data in children up to 24 months of age [see Adverse Reactions (6.1), Clinical Pharmacology (12.3), and Clinical Studies (14) in the full prescribing information]. The safety and effectiveness of BEYFORTUS have not been established in children older than 24 months of age. 10 OVERDOSAGE There is limited experience of overdose with BEYFORTUS. There is no specific treatment for an overdose with BEYFORTUS. In the event of an overdose, the individual should be monitored for the occurrence of adverse reactions and provided with symptomatic treatment as appropriate. Manufactured by: AstraZeneca AB, Södertälje, Sweden SE-15185 US License No. 2059 Distributed by: Sanofi Pasteur, Inc., Swiftwater, PA 18370 USA BEYFORTUS is a trademark of the Sanofi group of companies. ©AstraZeneca 2023 NIR-BPLR-SL-JUL23 Revised: July 2023 BEYFORTUS™ (nirsevimab-alip) injection, for intramuscular use

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