Safety and Efficacy of Combination SARS-CoV-2 Neutralizing Monoclonal Antibodies Amubarvimab Plus Romlusevimab in Nonhospitalized Patients With COVID-19. Academic Article uri icon

Overview

abstract

  • BACKGROUND: Development of safe and effective SARS-CoV-2 therapeutics is a high priority. Amubarvimab and romlusevimab are noncompeting anti-SARS-CoV-2 monoclonal antibodies with an extended half-life. OBJECTIVE: To assess the safety and efficacy of amubarvimab plus romlusevimab. DESIGN: Randomized, placebo-controlled, phase 2 and 3 platform trial. (ClinicalTrials.gov: NCT04518410). SETTING: Nonhospitalized patients with COVID-19 in the United States, Brazil, South Africa, Mexico, Argentina, and the Philippines. PATIENTS: Adults within 10 days onset of symptomatic SARS-CoV-2 infection who are at high risk for clinical progression. INTERVENTION: Combination of monoclonal antibodies amubarvimab plus romlusevimab or placebo. MEASUREMENTS: Nasopharyngeal and anterior nasal swabs for SARS-CoV-2, COVID-19 symptoms, safety, and progression to hospitalization or death. RESULTS: Eight-hundred and seven participants who initiated the study intervention were included in the phase 3 analysis. Median age was 49 years (quartiles, 39 to 58); 51% were female, 18% were Black, and 50% were Hispanic or Latino. Median time from symptom onset at study entry was 6 days (quartiles, 4 to 7). Hospitalizations and/or death occurred in 9 (2.3%) participants in the amubarvimab plus romlusevimab group compared with 44 (10.7%) in the placebo group, with an estimated 79% reduction in events (P < 0.001). This reduction was similar between participants with 5 or less and more than 5 days of symptoms at study entry. Grade 3 or higher treatment-emergent adverse events through day 28 were seen less frequently among participants randomly assigned to amubarvimab plus romlusevimab (7.3%) than placebo (16.1%) (P < 0.001), with no severe infusion reactions or drug-related serious adverse events. LIMITATION: The study population was mostly unvaccinated against COVID-19 and enrolled before the spread of Omicron variants and subvariants. CONCLUSION: Amubarvimab plus romlusevimab was safe and significantly reduced the risk for hospitalization and/or death among nonhospitalized adults with mild to moderate SARS-CoV-2 infection at high risk for progression to severe disease. PRIMARY FUNDING SOURCE: National Institute of Allergy and Infectious Diseases of the National Institutes of Health.

authors

  • Evering, Teresa
  • Chew, Kara W
  • Giganti, Mark J
  • Moser, Carlee
  • Pinilla, Mauricio
  • Wohl, David Alain
  • Currier, Judith S
  • Eron, Joseph J
  • Javan, Arzhang Cyrus
  • Bender Ignacio, Rachel
  • Margolis, David
  • Zhu, Qing
  • Ma, Ji
  • Zhong, Lijie
  • Yan, Li
  • D'Andrea Nores, Ulises
  • Hoover, Keila
  • Mocherla, Bharat
  • Choudhary, Manish C
  • Deo, Rinki
  • Ritz, Justin
  • Fischer, William A
  • Fletcher, Courtney V
  • Li, Jonathan Z
  • Hughes, Michael D
  • Smith, Davey
  • Daar, Eric S

publication date

  • April 18, 2023

Research

keywords

  • COVID-19

Identity

PubMed Central ID

  • PMC10150320

Scopus Document Identifier

  • 85159736445

Digital Object Identifier (DOI)

  • 10.1038/s41586-022-05644-7]

PubMed ID

  • 37068272

Additional Document Info

volume

  • 176

issue

  • 5