Lower Respiratory Tract Infections Following Respiratory Syncytial Virus Monoclonal Antibody Nirsevimab Immunization Versus Placebo: Analysis From a Phase 3 Randomized Clinical Trial (MELODY)
Douglas Arbetter, Vancheswaran Gopalakrishnan, Anastasia A. Aksyuk, Bahar Ahani, Yue Chang, Ron Dagan, Mark T. Esser, Laura L. Hammitt, Vaishali S. Mankad, Xavier Sáez‐Llorens, D. T. Shen, Amanda Leach, Elizabeth J. Kelly, Tonya Villafana, Deidre Wilkins
Abstract
BACKGROUND: Nirsevimab is an extended half-life, highly potent, anti-respiratory syncytial virus (RSV) fusion protein neutralizing monoclonal antibody with efficacy against RSV-associated medically attended (MA) lower respiratory tract infection (LRTI) in infants and medically vulnerable children (aged ≤24 months). This post hoc exploratory analysis examined the incidence of LRTI from RSV and other respiratory pathogens during MELODY: a 2:1 randomized, double-blind, placebo-controlled, phase 3 study of nirsevimab in healthy term and late preterm (ie, gestational age ≥35 weeks) infants entering their first RSV season. METHODS: A total of 3012 participants were randomized to nirsevimab (n = 2009) or placebo (n = 1003). Nasopharyngeal swabs were collected from infants who presented with an LRTI and tested for 22 different respiratory pathogens using the BioFire® Respiratory 2.1 Panel. Incidence of RSV and non-RSV MA-LRTIs through day 511 and LRTI severity were assessed. RESULTS: A total of 852 nasopharyngeal swabs were collected from 561 participants through day 511: 519 swabs from 337 nirsevimab participants and 333 swabs from 224 placebo participants. RSV and non-RSV infections were detected in 193 of 852 (22.7%) and 55 of 852 (64.7%) swabs, respectively. RSV infection rates were lower with nirsevimab compared with placebo, including RSV-rhinovirus/enterovirus coinfections. Rates of other viral infections were similar between study arms. Approximately 70% of single RSV infections and RSV coinfections were adjudicated as mild, and 26.2% of single RSV infections and 24.5% of RSV coinfections required hospitalization. CONCLUSIONS: Nirsevimab protected against RSV single and coinfections, with no evidence of replacement of RSV with other respiratory viruses. Clinical Trials Registration. NCT03979313.