Lower respiratory tract infections following respiratory syncytial virus monoclonal antibody nirsevimab immunization versus placebo: Analysis from a Phase 3 randomized clinical trial (MELODY)

Doug Arbetter; Vancheswaran Gopalakrishnan; Anastasia A Aksyuk; Bahar Ahani; Yue Chang; Ron Dagan; Mark T Esser; Laura L Hammitt; Vaishali S Mankad; Xavier Saez-Llorens; David Shen; Amanda Leach; Elizabeth J Kelly; Tonya Villafana; Deidre Wilkins

doi:10.1093/cid/ciae596

Lower respiratory tract infections following respiratory syncytial virus monoclonal antibody nirsevimab immunization versus placebo: Analysis from a Phase 3 randomized clinical trial (MELODY)

Clin Infect Dis. 2024 Dec 4:ciae596. doi: 10.1093/cid/ciae596. Online ahead of print.

Authors

Doug Arbetter¹, Vancheswaran Gopalakrishnan², Anastasia A Aksyuk³, Bahar Ahani², Yue Chang⁴, Ron Dagan⁵, Mark T Esser⁶, Laura L Hammitt⁷, Vaishali S Mankad⁸, Xavier Saez-Llorens^{9

10

11}, David Shen¹, Amanda Leach¹², Elizabeth J Kelly³, Tonya Villafana⁶, Deidre Wilkins³

Affiliations

¹ Biometrics, Vaccines & Immune Therapies, BioPharmaceuticals R&D, AstraZeneca, Boston, MA, USA.
² Bioinformatics, Vaccines & Immune Therapies, BioPharmaceuticals R&D, AstraZeneca, Gaithersburg, MD, USA.
³ Translational Medicine, Vaccines & Immune Therapies, BioPharmaceuticals R&D, AstraZeneca, Gaithersburg, MD, USA.
⁴ Biometrics, Vaccines & Immune Therapies, BioPharmaceuticals R&D, AstraZeneca, Gaithersburg, MD, USA.
⁵ The Shraga Segal Dept. of Microbiology, Immunology and Genetics, Faculty of Health Sciences of the Ben-Gurion University of the Negev, Beer-Sheva, Israel.
⁶ Vaccines & Immune Therapies, BioPharmaceuticals R&D, AstraZeneca, Gaithersburg, MD, USA.
⁷ Department of International Health, Johns Hopkins University, Baltimore, MD, USA.
⁸ Clinical Development, Respiratory & Immunology, BioPharmaceuticals R&D, AstraZeneca, Durham, NC, USA.
⁹ Cevaxin Research Center, Panama City, Panama.
¹⁰ Department of Infectious Diseases, Hospital del Niño Dr José Renán Esquivel, Panama City, Panama.
¹¹ SNI, National Secretariat of Science, Technology and Innovation (SENACYT), Panama City, Panama.
¹² Clinical Development, Vaccines & Immune Therapies, BioPharmaceuticals R&D, AstraZeneca, Gaithersburg, MD, USA.

PMID: 39656748
DOI: 10.1093/cid/ciae596

Abstract

Background: Nirsevimab is an extended half-life, highly potent neutralizing monoclonal antibody against the respiratory syncytial virus (RSV) fusion protein, with efficacy in preventing 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 a 2:1 randomized, double-blind, placebo-controlled, phase 3 study of nirsevimab, in healthy-term and late-preterm (i.e. gestational age ≥35 weeks) infants entering their first RSV season (MELODY).

Methods: 3012 participants were randomized to nirsevimab (n = 2009) or placebo (n = 1003). Nasopharyngeal swabs were collected from infants presenting 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 per the ReSViNET scale were assessed.

Results: 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 193/852 (22.7%) and 551/852 (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.

Trial registration: ClinicalTrials.gov NCT03979313.

Keywords: Lower respiratory tract infection; RSV immunization; nirsevimab; preterm infants; respiratory viruses; term infants.

Associated data

ClinicalTrials.gov/NCT03979313