Beyfortus - Drug Monograph

Introduction

Beyfortus (nirsevimab-alip) is a long-acting monoclonal antibody approved for the prevention of respiratory syncytial virus (RSV) lower respiratory tract disease in neonates and infants. Developed through a collaboration between AstraZeneca and Sanofi, it represents a significant advancement in RSV prevention, offering protection throughout the entire RSV season with a single dose.

Mechanism of Action

Nirsevimab-alip is a recombinant human immunoglobulin G1 kappa (IgG1κ) monoclonal antibody that binds to the prefusion conformation of the RSV fusion (F) protein. This binding neutralizes RSV by preventing viral entry into host cells and subsequent syncytium formation. Unlike palivizumab, which targets both pre- and post-fusion F protein conformations, nirsevimab specifically targets the prefusion conformation with higher affinity, resulting in enhanced neutralization potency and extended half-life.

Indications

• Prevention of RSV lower respiratory tract disease in:

- All infants during their first RSV season - Children up to 24 months of age who remain vulnerable to severe RSV disease through their second RSV season

Approved by the FDA in July 2023 and EMA in October 2022.

Dosage and Administration

• Infants weighing <5 kg: 50 mg single intramuscular injection
• Infants weighing ≥5 kg: 100 mg single intramuscular injection

• Administer intramuscularly preferably before or during the RSV season
• May be administered concurrently with age-appropriate vaccinations
• Do not administer intravenously

• No dosage adjustment required for renal or hepatic impairment
• Safety in preterm infants (<29 weeks gestational age) established in clinical trials

Pharmacokinetics

Contraindications

• History of severe hypersensitivity reaction to nirsevimab or any component of the formulation
• No other absolute contraindications identified

Warnings and Precautions

Drug Interactions

• No formal drug interaction studies conducted
• Theoretical potential for interference with live virus vaccines, though clinical data show no interference with routine vaccinations
• No expected interactions with cytochrome P450 substrates

Adverse Effects

• Rash (1.6%)
• Injection site reactions (1.2% including erythema, swelling, pain)
• Fever (0.9%)

• Hypersensitivity reactions (<0.1%)
• Anaphylaxis (very rare)

Monitoring Parameters

• Observe for hypersensitivity reactions for appropriate period post-administration
• Monitor for signs of RSV infection despite prophylaxis
• No routine laboratory monitoring required

Patient Education

• Beyfortus provides protection against RSV for the entire season with one dose
• It is not a vaccine but provides immediate protection
• Normal vaccination schedule should be maintained
• Contact healthcare provider if signs of severe allergic reaction occur (difficulty breathing, swelling of face/lips/tongue, severe rash)
• Protection begins immediately after administration

References

1. FDA Approval Package: Nirsevimab (Beyfortus). July 2023 2. Griffin MP et al. Single-Dose Nirsevimab for Prevention of RSV in Preterm Infants. NEJM 2020;383:415-425 3. Hammitt LL et al. Nirsevimab for Prevention of RSV in Healthy Late-Preterm and Term Infants. NEJM 2022;386:837-846 4. EMA Assessment Report: Beyfortus. October 2022 5. American Academy of Pediatrics. Updated Guidance for Use of Palivizumab and Nirsevimab. Pediatrics 2023;152(1):e2023063677 6. Muller WJ et al. Nirsevimab for Prevention of RSV in Infants. Expert Rev Anti Infect Ther 2023;21(5):455-466