Single-Dose Nirsevimab for Prevention of RSV in Preterm Infants

N Engl J Med. 2020 Jul 30;383(5):415-425. doi: 10.1056/NEJMoa1913556.

Abstract

Background: Respiratory syncytial virus (RSV) is the most common cause of lower respiratory tract infection in infants, and a need exists for prevention of RSV in healthy infants. Nirsevimab is a monoclonal antibody with an extended half-life that is being developed to protect infants for an entire RSV season with a single intramuscular dose.

Methods: In this trial conducted in both northern and southern hemispheres, we evaluated nirsevimab for the prevention of RSV-associated lower respiratory tract infection in healthy infants who had been born preterm (29 weeks 0 days to 34 weeks 6 days of gestation). We randomly assigned the infants in a 2:1 ratio to receive nirsevimab, at a dose of 50 mg in a single intramuscular injection, or placebo at the start of an RSV season. The primary end point was medically attended RSV-associated lower respiratory tract infection through 150 days after administration of the dose. The secondary efficacy end point was hospitalization for RSV-associated lower respiratory tract infection through 150 days after administration of the dose.

Results: From November 2016 through November 2017, a total of 1453 infants were randomly assigned to receive nirsevimab (969 infants) or placebo (484 infants) at the start of the RSV season. The incidence of medically attended RSV-associated lower respiratory tract infection was 70.1% lower (95% confidence interval [CI], 52.3 to 81.2) with nirsevimab prophylaxis than with placebo (2.6% [25 infants] vs. 9.5% [46 infants]; P<0.001) and the incidence of hospitalization for RSV-associated lower respiratory tract infection was 78.4% lower (95% CI, 51.9 to 90.3) with nirsevimab than with placebo (0.8% [8 infants] vs. 4.1% [20 infants]; P<0.001). These differences were consistent throughout the 150-day period after the dose was administered and across geographic locations and RSV subtypes. Adverse events were similar in the two trial groups, with no notable hypersensitivity reactions.

Conclusions: A single injection of nirsevimab resulted in fewer medically attended RSV-associated lower respiratory tract infections and hospitalizations than placebo throughout the RSV season in healthy preterm infants. (Funded by AstraZeneca and Sanofi Pasteur; ClinicalTrials.gov number, NCT02878330.).

Publication types

  • Multicenter Study
  • Randomized Controlled Trial
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Antibodies, Monoclonal / administration & dosage*
  • Antibodies, Monoclonal / adverse effects
  • Antibodies, Monoclonal, Humanized / administration & dosage*
  • Antibodies, Monoclonal, Humanized / adverse effects
  • Antiviral Agents / administration & dosage*
  • Antiviral Agents / adverse effects
  • Female
  • Hospitalization / statistics & numerical data
  • Humans
  • Incidence
  • Infant
  • Infant, Newborn
  • Infant, Premature*
  • Injections, Intramuscular
  • Kaplan-Meier Estimate
  • Male
  • Poisson Distribution
  • Respiratory Syncytial Virus Infections / epidemiology
  • Respiratory Syncytial Virus Infections / prevention & control*
  • Respiratory Syncytial Virus, Human*
  • Respiratory Tract Infections / epidemiology
  • Respiratory Tract Infections / prevention & control*
  • Respiratory Tract Infections / virology
  • Viral Fusion Proteins / antagonists & inhibitors*

Substances

  • Antibodies, Monoclonal
  • Antibodies, Monoclonal, Humanized
  • Antiviral Agents
  • F protein, human respiratory syncytial virus
  • Viral Fusion Proteins
  • nirsevimab

Associated data

  • ClinicalTrials.gov/NCT02878330