REGEN-COV Antibody Combination and Outcomes in Outpatients with Covid-19

N Engl J Med. 2021 Dec 2;385(23):e81. doi: 10.1056/NEJMoa2108163. Epub 2021 Sep 29.

Abstract

Background: In the phase 1-2 portion of an adaptive trial, REGEN-COV, a combination of the monoclonal antibodies casirivimab and imdevimab, reduced the viral load and number of medical visits in patients with coronavirus disease 2019 (Covid-19). REGEN-COV has activity in vitro against current severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) variants of concern.

Methods: In the phase 3 portion of an adaptive trial, we randomly assigned outpatients with Covid-19 and risk factors for severe disease to receive various doses of intravenous REGEN-COV or placebo. Patients were followed through day 29. A prespecified hierarchical analysis was used to assess the end points of hospitalization or death and the time to resolution of symptoms. Safety was also evaluated.

Results: Covid-19-related hospitalization or death from any cause occurred in 18 of 1355 patients in the REGEN-COV 2400-mg group (1.3%) and in 62 of 1341 patients in the placebo group who underwent randomization concurrently (4.6%) (relative risk reduction [1 minus the relative risk], 71.3%; P<0.001); these outcomes occurred in 7 of 736 patients in the REGEN-COV 1200-mg group (1.0%) and in 24 of 748 patients in the placebo group who underwent randomization concurrently (3.2%) (relative risk reduction, 70.4%; P = 0.002). The median time to resolution of symptoms was 4 days shorter with each REGEN-COV dose than with placebo (10 days vs. 14 days; P<0.001 for both comparisons). REGEN-COV was efficacious across various subgroups, including patients who were SARS-CoV-2 serum antibody-positive at baseline. Both REGEN-COV doses reduced viral load faster than placebo; the least-squares mean difference in viral load from baseline through day 7 was -0.71 log10 copies per milliliter (95% confidence interval [CI], -0.90 to -0.53) in the 1200-mg group and -0.86 log10 copies per milliliter (95% CI, -1.00 to -0.72) in the 2400-mg group. Serious adverse events occurred more frequently in the placebo group (4.0%) than in the 1200-mg group (1.1%) and the 2400-mg group (1.3%); infusion-related reactions of grade 2 or higher occurred in less than 0.3% of the patients in all groups.

Conclusions: REGEN-COV reduced the risk of Covid-19-related hospitalization or death from any cause, and it resolved symptoms and reduced the SARS-CoV-2 viral load more rapidly than placebo. (Funded by Regeneron Pharmaceuticals and others; ClinicalTrials.gov number, NCT04425629.).

Publication types

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

MeSH terms

  • Adolescent
  • Adult
  • Antibodies, Monoclonal, Humanized / administration & dosage*
  • Antibodies, Monoclonal, Humanized / pharmacokinetics
  • Antibodies, Monoclonal, Humanized / pharmacology
  • Antibodies, Neutralizing / administration & dosage*
  • Antibodies, Neutralizing / pharmacology
  • Antiviral Agents / administration & dosage*
  • Antiviral Agents / pharmacokinetics
  • Antiviral Agents / pharmacology
  • COVID-19 / drug therapy*
  • COVID-19 / mortality
  • Dose-Response Relationship, Drug
  • Double-Blind Method
  • Drug Combinations
  • Female
  • Hospitalization / statistics & numerical data
  • Humans
  • Kaplan-Meier Estimate
  • Male
  • Middle Aged
  • Pregnancy
  • Pregnancy Complications, Infectious / drug therapy
  • Proportional Hazards Models
  • Viral Load / drug effects
  • Young Adult

Substances

  • Antibodies, Monoclonal, Humanized
  • Antibodies, Neutralizing
  • Antiviral Agents
  • Drug Combinations
  • casirivimab and imdevimab drug combination

Associated data

  • ClinicalTrials.gov/NCT04425629