What are the therapeutic alternatives to Enflonsia (clesrovimab) for preventing Respiratory Syncytial Virus (RSV) lower respiratory tract disease in neonates and infants born during or entering their first RSV season?

Therapeutic Alternatives to Enflonsia (Clesrovimab) for RSV Prevention in Infants

Nirsevimab (Beyfortus) is the primary therapeutic alternative to Enflonsia (clesrovimab) for preventing RSV lower respiratory tract disease in neonates and infants during their first RSV season. 1, 2, 3

Primary Alternative: Nirsevimab (Beyfortus)

Efficacy and Administration

• Single intramuscular injection providing protection throughout the RSV season (typically October through March in most of continental US)
• Demonstrated 79.0% efficacy in preventing medically attended RSV-associated LRTI and 80.6% efficacy in preventing RSV-associated hospitalizations 1
• Dosing based on infant weight:
  • Less than 5 kg: 50 mg
  • 5 kg and greater: 100 mg 3
• Protection lasts approximately 150 days after injection 4, 5

Eligibility

• Recommended for all infants aged <8 months who are born during or entering their first RSV season
• Also recommended for infants and children aged 8-19 months who are at increased risk for severe RSV disease entering their second RSV season 2
• Use chronologic (not corrected) age for preterm infants to determine timing and eligibility 2

Maternal Vaccination Alternative

• RSVpreF vaccine (Abrysvo) administered to pregnant persons at 32 weeks 0 days–36 weeks 6 days gestation provides passive immunity to infants from birth 2
• Can be administered during September–January in most of continental US
• Can be co-administered with other recommended vaccines during pregnancy (Tdap, influenza, COVID-19) without timing restrictions 2

Limited Alternative: Palivizumab

• Prior to nirsevimab and clesrovimab, palivizumab was the only FDA-approved product for RSV prevention
• Limitations include:
  • Requires monthly injections throughout the RSV season
  • Higher cost
  • Recommended only for children with specific underlying medical conditions (comprising <5% of all infants) 1
• American Academy of Pediatrics recommendations limit use to specific high-risk groups:
  • Infants with chronic lung disease requiring medical therapy
  • Infants with hemodynamically significant congenital heart disease
  • Certain preterm infants 1, 6

Decision Algorithm for RSV Prevention

1. First consideration: Has the mother received RSVpreF vaccine during pregnancy?

   • If YES: No additional RSV prophylaxis needed for most infants
   • If NO: Proceed to step 2

2. For infants without maternal protection:

   • Either nirsevimab or clesrovimab is recommended
   • No specific product preference between these two monoclonal antibodies 7
   • Selection should be based on:
     • Product availability
     • Parent preference
     • Timing of infant's birth relative to RSV season 7

3. For high-risk infants entering second RSV season:

   • Nirsevimab is recommended for those aged 8-19 months with:
     • Chronic lung disease of prematurity
     • Severe immunocompromise
     • Cystic fibrosis
     • American Indian or Alaska Native children 2

Non-Pharmacological Prevention Measures

• Keep high-risk infants away from crowds and situations with potential exposure to infected people
• Restrict participation in group child care during RSV season when feasible
• Practice careful hand hygiene
• Ensure all age-appropriate immunizations are current, including influenza vaccine for infants ≥6 months and their contacts 1
• Eliminate exposure to tobacco smoke 6

Clinical Considerations

• RSV is the leading cause of hospitalization among US infants, with 50,000-80,000 RSV-associated hospitalizations and 100-300 deaths annually 1, 2
• 79% of infants and children aged <2 years hospitalized with RSV have no underlying medical conditions 1
• The rate of RSV-associated hospitalization among infants born at ≤30 weeks' gestation is three times that of term infants 1
• Both nirsevimab and clesrovimab provide significant protection with a single dose, overcoming the limitations of monthly palivizumab administration 7, 4, 5