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

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.).

Copyright © 2021 Massachusetts Medical Society.

Figures

Figure 1. Screening, Randomization, Treatment, and Analysis.

In the original phase 3 portion of the trial, Regeneron requested that 2, 1, and 5 patients in the placebo, REGEN-COV 2400-mg, and REGEN-COV 8000-mg groups, respectively, withdraw from the trial because these patients underwent randomization in error. In the amended phase 3 portion of the trial, Regeneron requested that 2, 4, and 2 patients in the placebo, REGEN-COV 1200-mg, and REGEN-COV 2400-mg groups, respectively, withdraw from the trial because these patients underwent randomization in error. The modified full analysis set included all patients who were confirmed by means of quantitative reverse-transcriptase–polymerase-chain-reaction testing at a central laboratory to be positive for severe acute respiratory syndrome coronavirus 2 at baseline and who had at least one risk factor for severe coronavirus disease 2019 (Covid-19).

Figure 2. Clinical Efficacy.

Panel A shows the percentage of patients who were hospitalized or died from any cause in the amended phase 3 portion of the trial. Panel B shows the percentage of patients who were hospitalized or died from any cause in the original and amended phase 3 portions of the trial combined. Panel C shows the time to resolution of symptoms in the amended phase 3 portion of the trial. The lower and upper confidence limits are shown.