Positive results were announced from the phase 3 MELODY and phase 2/3 MEDLEY trials evaluating nirsevimab for prevention of medically-attended respiratory syncytial virus (RSV)-confirmed lower respiratory tract infection in infants entering their first RSV season.
Nirsevimab is a long-acting anti-RSV monoclonal antibody that has an extended half-life. The randomized, double-blind, placebo-controlled MELODY trial (ClinicalTrials.gov Identifier: NCT03979313) evaluated the efficacy and safety of nirsevimab in 1490 healthy infants who were born at a gestational age of at least 35 weeks.
Patients were randomly assigned 2:1 to receive a single intramuscular injection of nirsevimab 50mg (for infants weighing less than 5kg) or 100mg (for infants weighing at least 5kg), or placebo before the start of an RSV season. The primary endpoint was the incidence of medically-attended RSV-associated lower respiratory tract infection (LRTI) through 150 days after the injection.
Findings showed that treatment with nirsevimab was associated with a 74.5% (95% CI, 49.6-87.1; P <.001) reduction in the incidence of medically-attended RSV-associated LRTI compared with placebo (1.2% vs 5.0%, respectively). Additionally, a lower incidence of hospitalization for RSV-associated LRTI was observed in the nirsevimab arm compared with the placebo arm (0.6% vs 1.6%, respectively; efficacy: 62.1% [95% CI, -8.6, 86.8; P =.07).
“These exciting data show that nirsevimab has the potential to offer RSV protection for all infants, which would be a paradigm shift in the approach to this disease,” said Dr William Muller, Associate Professor, Pediatrics, Northwestern University Feinberg School of Medicine and Scientific Director, Clinical and Community Trials, Ann & Robert H. Lurie Children’s Hospital of Chicago, Illinois, US and primary investigator of the MELODY phase 3 trial.
In the randomized, double-blind, phase 2/3 MEDLEY trial (ClinicalTrials.gov Identifier: NCT03959488), the safety and tolerability of nirsevimab was compared with palivizumab in approximately 925 infants with congenital heart disease, chronic lung disease, and/or prematurity before entering their first RSV season. Findings showed that nirsevimab demonstrated a similar safety and tolerability profile compared with palivizumab.
Commenting on the findings, Mene Pangalos, Executive Vice President, BioPharmaceuticals R&D, AstraZeneca, said: “These data show for the first time, the potential to significantly protect all infants through their first respiratory syncytial virus season with a single dose immunization and we look forward to working with health authorities to bring nirsevimab to infants as quickly as possible.”
- Nirsevimab significantly protected infants against RSV disease in phase III MELODY trial. News release. AstraZeneca. Accessed March 3, 2022. https://www.astrazeneca.com/media-centre/press-releases/2022/nirsevimab-significantly-protected-infants-against-rsv-disease-in-phase-iii-melody-trial.html.
- Hammitt LL, Dagan R, Yuan Y, et al. Nirsevimab for prevention of RSV in healthy late-preterm and term infants. N Engl J Med. Published online March 3, 2022. doi: 10.1056/NEJMoa2110275.