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

Ann Intern Med. 2023 May;176(5):658-666. doi: 10.7326/M22-3428. Epub 2023 Apr 18.

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.

Publication types

  • Randomized Controlled Trial
  • Research Support, N.I.H., Extramural

MeSH terms

  • Adult
  • Antibodies, Monoclonal
  • Antibodies, Viral
  • COVID-19*
  • Double-Blind Method
  • Female
  • Humans
  • Male
  • Middle Aged
  • SARS-CoV-2

Substances

  • romlusevimab
  • amubarvimab
  • Antibodies, Monoclonal
  • Antibodies, Viral

Supplementary concepts

  • SARS-CoV-2 variants

Associated data

  • ClinicalTrials.gov/NCT04518410