What are the key points to know about Beyfortus (nirsevimab) pharmacology?

Key Pharmacology of Beyfortus (Nirsevimab)

Beyfortus (nirsevimab) is a long-acting monoclonal antibody that provides passive immunity against respiratory syncytial virus (RSV) with a single intramuscular dose that protects infants throughout the entire 5-month RSV season. 1, 2

Mechanism of Action

• Nirsevimab-alip is a recombinant human IgG1κ monoclonal antibody that targets the prefusion conformation of the RSV F protein, preventing viral entry by inhibiting fusion of viral and cellular membranes 2
• It contains a triple amino acid substitution (YTE) in the Fc region that increases binding to the neonatal Fc receptor, extending its serum half-life 2
• Nirsevimab binds to a conserved epitope in antigenic site Ø on the prefusion protein with high affinity (KD = 0.12 nM for RSV-A and KD = 1.22 nM for RSV-B) 2

Pharmacokinetics

• Absorption: Bioavailability is approximately 84% with median time to maximum concentration of 6 days (range 1-28 days) after intramuscular injection 2
• Distribution: Total volume of distribution is 477 mL for an infant weighing 5 kg 2
• Elimination: Terminal half-life is approximately 71 days with estimated clearance of 3.42 mL/day for a 5 kg infant 2
• Metabolism: Degraded into small peptides through normal catabolic pathways 2
• Duration of Protection: A single dose provides protection for 5 months, covering the entire RSV season 2

Clinical Efficacy

• Reduces medically attended RSV-associated lower respiratory tract infections by 70.1-74.5% in preterm and term infants 3, 4
• Reduces RSV-associated hospitalizations by 78.4-83.2% compared to placebo or standard care 3, 5
• Efficacy demonstrated across different geographic locations and against both RSV subtypes A and B 3
• Protection against very severe RSV-associated lower respiratory tract infections with efficacy of 75.7% 5

Dosing Recommendations

• Administered as a single intramuscular injection shortly before or during the RSV season (typically fall through spring) 1
• Recommended for all infants aged <8 months who are born during or entering their first RSV season 1
• Also recommended for infants and children aged 8–19 months who are at increased risk for severe RSV disease and are entering their second RSV season 1

Special Populations

• No clinically significant differences in pharmacokinetics based on race or vulnerability to severe RSV disease (i.e., chronic lung disease, congenital heart disease, gestational age <29 weeks) 2
• High-risk populations for second-season dosing include:
  • Children with chronic lung disease of prematurity requiring medical support 1
  • Children with severe immunocompromise 1
  • Children with cystic fibrosis with severe lung disease or poor growth 1
  • American Indian or Alaska Native children 1

Safety Profile

• Similar adverse event profile compared to placebo in clinical trials 3, 4
• Treatment-related adverse events occurred in 2.1% of infants receiving nirsevimab in real-world settings 5
• Contraindicated in persons with history of severe allergic reaction (e.g., anaphylaxis) to a previous dose or product component 1
• Can be co-administered with routine childhood vaccines with similar safety and reactogenicity profile to vaccines given alone 2

Clinical Considerations

• Antidrug antibodies were detected in 6.1% of infants receiving nirsevimab versus 1.1% in placebo group by day 361 4
• No formal drug interaction studies have been performed, but nirsevimab is not predicted to interact with cytochrome P450 enzymes or transporter systems 2
• Adverse events should be reported to FDA MedWatch or to VAERS if co-administered with vaccines 1

Advantages Over Previous Prophylaxis

• Unlike palivizumab, nirsevimab requires only a single dose for the entire RSV season rather than monthly injections 1, 6
• Recommended for all infants, not just those with specific risk factors, addressing the fact that 79% of infants hospitalized with RSV have no underlying medical conditions 1, 6