The European Commission (EC) has approved AstraZeneca and Sanofi’s Beyfortus® (nirsevimab) for the prevention of respiratory syncytial virus (RSV) lower respiratory tract disease in newborns and infants during their first RSV season. Nirsevimab is human IgG1ҡ antibody targeting RSV. The Fc domain was engineered using AstraZeneca’s proprietary YTE half-life extension technology. Developed by AstraZeneca and Sanofi, nirsevimab is designed to offer newborns and infants direct protection against RSV and help prevent RSV-related lower respiratory tract infections.
Nirsevimab received regulatory designations to facilitate development, including a Promising Innovative Medicine designation from the UK Medicines and Healthcare Products Regulatory Agency; Breakthrough Therapy designation from China’s NMPA; Breakthrough Therapy designation from FDA; and PRIME designation from EMA. In addition, it was named “a medicine for prioritized development” under the Project for Drug Selection to Promote New Drug Development in Pediatrics by Japan’s Agency for Medical Research and Development. The approval by the EC was based on results of the Phase 3 MELODY (NCT03979313), Phase 2/3 MEDLEY (NCT03959488), and Phase 2b (NCT02878330) clinical trials.
The Phase 2b trial is a randomized, placebo-controlled trial designed to measure the efficacy of nirsevimab in preventing medically attended RSV-related lower respiratory tract infections through 150 days post-dose. The study was conducted on healthy preterm infants (29–35 weeks’ gestation) who were randomized (2:1) to receive a single intramuscular injection of nirsevimab (50 mg) or placebo. The primary endpoint of the study was met, with a reduction of the incidence of medically attended RSV-related lower respiratory tract infections by 70.1% (95% CI: 52.3, 81.2) compared to placebo.
MELODY is a randomized, placebo-controlled Phase 3 trial evaluating the safety and efficacy of nirsevimab for the prevention of medically attended lower respiratory tract infections in healthy late preterm and term infants (i.e., born at 35 weeks’ gestation or later). Participants (n=1490) up to 1 y of age were randomized (2:1) to receive a single intramuscular injection of nirsevimab (50 mg if <5 kg or 100 mg if >5 kg body weight) or placebo. The primary endpoint of this study was met, with a reduction in the incidence of medically attended lower respiratory tract infections caused by RSV of 74.5% (95% CI 49.6, 87.1; P<0.001) compared to placebo.
The randomized, double-blind, palivizumab-controlled Phase 2/3 MEDLEY study evaluated the safety and pharmacokinetics of nirsevimab compared to palivizumab in preterm infants and infants with congenital heart disease and/or chronic lung disease of prematurity eligible to receive palivizumab entering their first RSV season. Participants (n=925) up to 1 year of age entering their first RSV season were randomized to receive a single intramuscular injection of nirsevimab or palivizumab (50 mg if <5 kg or 100 mg if >5 kg body weight). Safety was assessed by monitoring the occurrence of treatment-emergent adverse events or treatment-emergent serious adverse events through 360 days post-dose. Serum levels of nirsevimab following dosing (on day 151) in this trial were comparable with those observed in the MELODY study, suggesting a similar protection in this population to that in the healthy term and late preterm infants.