Nirsevimab

BEYFORTUS is indicated for the prevention of Respiratory Syncytial Virus (RSV) lower respiratory tract disease in: Neonates and infants born during or entering their first RSV season. Children up to 24 months of age who remain vulnerable to severe RSV disease through their second RSV season. BEYFORTUS is a respiratory syncytial virus (RSV) F protein-directed fusion inhibitor indicated for the prevention of RSV lower respiratory tract disease in: Neonates and infants born during or entering their first RSV season. ( 1 ) Children up to 24 months of age who remain vulnerable to severe RSV disease through their second RSV season. ( 1 )

BEYFORTUS is a clear to opalescent, colorless to yellow solution available as follows: Injection: 50 mg/0.5 mL in a single-dose pre-filled syringe. Injection: 100 mg/mL in a single-dose pre-filled syringe. Injection: 50 mg/0.5 mL in a single-dose pre-filled syringe. ( 3 ) 100 mg/mL in a single-dose pre-filled syringe. ( 3 )

BEYFORTUS is contraindicated in infants and children with a history of serious hypersensitivity reactions, including anaphylaxis, to nirsevimab-alip or to any of the excipients [see Warnings and Precautions (5.1) and Description (11) ] . BEYFORTUS is contraindicated in infants and children with a history of serious hypersensitivity reactions, including anaphylaxis, to nirsevimab-alip or to any of the excipients. ( 4 )

Hypersensitivity Reactions Including Anaphylaxis: Serious hypersensitivity reactions have been reported following BEYFORTUS administration. These reactions included urticaria, dyspnea, cyanosis, and/or hypotonia. Anaphylaxis has been observed with human immunoglobulin G1 (IgG1) monoclonal antibodies. If signs and symptoms of anaphylaxis or other clinically significant hypersensitivity reactions occur, initiate appropriate treatment. ( 5.1 )

5.1 Hypersensitivity Reactions Including Anaphylaxis Serious hypersensitivity reactions have been reported following BEYFORTUS administration. These reactions included urticaria, dyspnea, cyanosis, and/or hypotonia. Anaphylaxis has been observed with human immunoglobulin G1 (IgG1) monoclonal antibodies. If signs and symptoms of anaphylaxis or other clinically significant hypersensitivity reactions occur, initiate appropriate treatment.

5.2 Use in Individuals with Clinically Significant Bleeding Disorders As with any other IM injections, BEYFORTUS should be given with caution to infants and children with thrombocytopenia, any coagulation disorder, or to individuals on anticoagulation therapy.

Most common adverse reactions were rash (0.9%) and injection site reactions (0.3%). ( 6.1 ) To report SUSPECTED ADVERSE REACTIONS, contact Sanofi at 1-855-239-3678 or FDA at 1-800-FDA-1088 or www.fda.gov/medwatch.

6.1 Clinical Trials Experience 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. Table 3 Adverse Reactions Reported at an Incidence Higher Than Placebo in the Safety Population 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. (Trials 03 and 04) Adverse Reaction BEYFORTUS N=2,570 % Placebo N=1,284 % Rash Rash was defined by the following grouped preferred terms: rash, rash macular, rash maculo-papular, rash papular. (occurring within 14 days post-dose) 0.9

0.6 Injection site reaction 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. (occurring within 7 days post-dose) 0.3 0 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. Term and Preterm Infants Entering Their First RSV Season (Trial 09) The safety of BEYFORTUS was evaluated in Trial 09, a randomized open-label multicenter trial in 8,034 term and preterm infants (GA greater than or equal to 29 weeks) entering their first RSV season (not eligible for palivizumab), who received BEYFORTUS (N=4,016) or no intervention (N=4,018) for the prevention of RSV LRTI hospitalization. Subjects were followed for 365 days post-dose (BEYFORTUS arm) or post-randomization (no intervention arm) to assess safety. The safety profile of BEYFORTUS administered in the first RSV season was consistent with the safety profile of BEYFORTUS in the placebo-controlled Trials 03 and 04.

6.2 Postmarketing Experience The following adverse reactions have been identified during post approval use of BEYFORTUS. […]

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.

The safety and effectiveness of BEYFORTUS in children older than 24 months of age have not been established. ( 8.4 )

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) ]. Use of BEYFORTUS in this population is supported by the following: – Trial 03, a randomized, double-blind, placebo-controlled multicenter trial for the prevention of MA RSV LRTI conducted in preterm infants born at GA greater than or equal to 29 weeks and less than 35 weeks entering their first RSV season; – Trial 04, a double-blind, placebo-controlled multicenter trial, for the prevention of MA RSV LRTI in term and late preterm infants GA greater than or equal to 35 weeks entering their first RSV season; – Trial 05, a Phase 2/3 randomized, double-blind, palivizumab-controlled multicenter trial in pediatric subjects born less than 35 weeks GA and infants with CLD of prematurity or hemodynamically significant CHD entering their first or second RSV season. In addition, BEYFORTUS was evaluated in an open-label, uncontrolled, single-dose trial (Trial 08) in 100 infants and children who were less than or equal to 24 months of age, who received BEYFORTUS in their first or second RSV season, and who had a wide variety of underlying diseases or treatments resulting in immune compromise. The safety profile of BEYFORTUS administered in Trial 08 was consistent with the safety profile of other trials of BEYFORTUS in infants and children [see Clinical Pharmacology (12.3) ]. Trial 09 is a Phase 3b randomized, open-label trial of BEYFORTUS compared to no intervention for the prevention of hospitalization in term and preterm infants (GA greater than or equal to 29 weeks) born during or entering their first RSV season [see Adverse Reactions (6.1) and Clinical Studies (14.5) ]. The safety and effectiveness of BEYFORTUS have not been established in children older than 24 months of age.

BEYFORTUS is a monoclonal antibody with anti-RSV activity [see Microbiology (12.4) ] .