Beyfortus Drug Information

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.

Recommended Dosage First RSV Season for Neonates and Infants

For neonates and infants born during the RSV season, administer BEYFORTUS starting from birth. For neonates and infants born outside the RSV season, administer BEYFORTUS once prior to the start of the RSV season considering duration of protection provided by BEYFORTUS. The recommended dosage of BEYFORTUS for neonates and infants born during or entering their first RSV season is based on body weight (see Table 1 ) and is administered as a single intramuscular (IM) injection.

Table 1 Second RSV Season for Children Who Remain at Increased Risk for Severe RSV Disease For children up to 24 months of age, regardless of body weight, who remain at increased risk for severe RSV disease in their second RSV season, refer to Table 2 below for recommended dosage. Table 2 Recommended Dosage of BEYFORTUS for the Second RSV Season for Children Who Remain at Increased Risk for Severe RSV Disease Child's Age at Time of Dosing Recommended Dosage Up to 24 months of age Regardless of body weight 200 mg administered as two IM injections of (2 × 100 mg) First and Second RSV Season for Children Undergoing Cardiac Surgery with Cardiopulmonary Bypass For children undergoing cardiac surgery with cardiopulmonary bypass, an additional dose of BEYFORTUS is recommended as soon as the child is stable after surgery to ensure adequate nirsevimab-alip serum levels. First RSV season: If surgery is within 90 days after receiving BEYFORTUS, the additional dose should be based on body weight at the time of the additional dose.

Refer to Table 1 for weight-based dosing. If more than 90 days have elapsed since receiving BEYFORTUS, the additional dose should be 50 mg regardless of body weight. Second RSV season: If surgery is within 90 days after receiving BEYFORTUS, the additional dose should be 200 mg, regardless of body weight.

Administration Instructions BEYFORTUS must be administered by a healthcare provider. Parenteral drug products should be inspected visually for particulate matter and discoloration prior to administration, whenever solution and container permit. BEYFORTUS is a clear to opalescent, colorless to yellow solution.

Do not inject BEYFORTUS if the liquid is cloudy, discolored, or it contains large particles or foreign particulate matter. Do not use if the BEYFORTUS pre-filled syringe has been dropped or damaged, the security seal on the carton has been broken, or the expiration date has passed. BEYFORTUS is available in a 50 mg and a 100 mg pre-filled syringe.

Check the labels on the BEYFORTUS carton and pre-filled syringe to ensure the correct 50 mg or 100 mg product is being used. Co-administration with Childhood Vaccines and Immunoglobulin Products BEYFORTUS can be given concomitantly with childhood vaccines. When administered concomitantly with injectable vaccines, they should be given with separate syringes and at different injection sites.

Do not mix BEYFORTUS with any vaccines or medications in the same syringe or vial. There is no information regarding co-administration of BEYFORTUS with other immunoglobulin products. Palivizumab should not be administered to infants who have already received BEYFORTUS in the same season.

There are no data regarding substitution of BEYFORTUS for palivizumab once prophylaxis treatment is initiated with palivizumab for the RSV season. BEYFORTUS may be administered prior to or during the second RSV season to children up to 24 months of age who remain vulnerable to severe RSV disease, and who received palivizumab in their first RSV season. Administration Instructions for Single-Dose Pre-filled Syringe BEYFORTUS 50 mg (50 mg/0.5 mL) pre-filled syringe with a purple plunger rod.

Refer to Figure 1 for pre-filled syringe components. Figure 1 Luer Lock Syringe Components Step 1: Holding the Luer lock in one hand (avoid holding the plunger rod or syringe body), unscrew the syringe cap by twisting it counter-clockwise with the other hand. Step 2: Attach a Luer lock needle to the pre-filled syringe by gently twisting the needle clockwise onto the pre-filled syringe until slight resistance is felt.

Step 3: Hold the syringe body with one hand and carefully pull the needle cover straight off with the other hand. Do not hold the plunger rod while removing the needle cover or the rubber stopper may move. Do not touch the needle or let it touch any surface.

Do not recap the needle or detach it from the syringe. Step 4: Administer the entire contents of the BEYFORTUS pre-filled syringe as an IM injection, preferably in the anterolateral aspect of the thigh. The gluteal muscle should not be used as an injection site because of the risk of damage to the sciatic nerve.

Step 5: Discard syringe into a sharps container. If two injections are required, repeat Steps 1–5 in a different injection site. Image Image Figure 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 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.

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 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).

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). 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) 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. 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.

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. 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.

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.

Postmarketing Experience

The following adverse reactions have been identified during post approval use of BEYFORTUS. Because these reactions are reported voluntarily from a population of uncertain size, it is not always possible to reliably estimate their frequency or establish a causal relationship to drug exposure. Hypersensitivity reactions.

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.

Pregnancy BEYFORTUS is not indicated for use in females of reproductive potential.

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.

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.

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

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.

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.