Lower Respiratory Tract Infections Following Respiratory Syncytial Virus Monoclonal Antibody Nirsevimab Immunization Versus Placebo: Analysis From a Phase 3 Randomized Clinical Trial (MELODY).

Abstract

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. 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. 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. Nirsevimab protected against RSV single and coinfections, with no evidence of replacement of RSV with other respiratory viruses. Clinical Trials Registration. NCT03979313.