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Clinical Trial
. 2021 Jan 21;384(3):238-251.
doi: 10.1056/NEJMoa2035002. Epub 2020 Dec 17.

REGN-COV2, a Neutralizing Antibody Cocktail, in Outpatients with Covid-19

David M Weinreich  1 , Sumathi Sivapalasingam  1 , Thomas Norton  1 , Shazia Ali  1 , Haitao Gao  1 , Rafia Bhore  1 , Bret J Musser  1 , Yuhwen Soo  1 , Diana Rofail  1 , Joseph Im  1 , Christina Perry  1 , Cynthia Pan  1 , Romana Hosain  1 , Adnan Mahmood  1 , John D Davis  1 , Kenneth C Turner  1 , Andrea T Hooper  1 , Jennifer D Hamilton  1 , Alina Baum  1 , Christos A Kyratsous  1 , Yunji Kim  1 , Amanda Cook  1 , Wendy Kampman  1 , Anita Kohli  1 , Yessica Sachdeva  1 , Ximena Graber  1 , Bari Kowal  1 , Thomas DiCioccio  1 , Neil Stahl  1 , Leah Lipsich  1 , Ned Braunstein  1 , Gary Herman  1 , George D Yancopoulos  1 ; Trial Investigators
Collaborators, Affiliations
Clinical Trial

REGN-COV2, a Neutralizing Antibody Cocktail, in Outpatients with Covid-19

David M Weinreich et al. N Engl J Med. .

Abstract

Background: Recent data suggest that complications and death from coronavirus disease 2019 (Covid-19) may be related to high viral loads.

Methods: In this ongoing, double-blind, phase 1-3 trial involving nonhospitalized patients with Covid-19, we investigated two fully human, neutralizing monoclonal antibodies against severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) spike protein, used in a combined cocktail (REGN-COV2) to reduce the risk of the emergence of treatment-resistant mutant virus. Patients were randomly assigned (1:1:1) to receive placebo, 2.4 g of REGN-COV2, or 8.0 g of REGN-COV2 and were prospectively characterized at baseline for endogenous immune response against SARS-CoV-2 (serum antibody-positive or serum antibody-negative). Key end points included the time-weighted average change in viral load from baseline (day 1) through day 7 and the percentage of patients with at least one Covid-19-related medically attended visit through day 29. Safety was assessed in all patients.

Results: Data from 275 patients are reported. The least-squares mean difference (combined REGN-COV2 dose groups vs. placebo group) in the time-weighted average change in viral load from day 1 through day 7 was -0.56 log10 copies per milliliter (95% confidence interval [CI], -1.02 to -0.11) among patients who were serum antibody-negative at baseline and -0.41 log10 copies per milliliter (95% CI, -0.71 to -0.10) in the overall trial population. In the overall trial population, 6% of the patients in the placebo group and 3% of the patients in the combined REGN-COV2 dose groups reported at least one medically attended visit; among patients who were serum antibody-negative at baseline, the corresponding percentages were 15% and 6% (difference, -9 percentage points; 95% CI, -29 to 11). The percentages of patients with hypersensitivity reactions, infusion-related reactions, and other adverse events were similar in the combined REGN-COV2 dose groups and the placebo group.

Conclusions: In this interim analysis, the REGN-COV2 antibody cocktail reduced viral load, with a greater effect in patients whose immune response had not yet been initiated or who had a high viral load at baseline. Safety outcomes were similar in the combined REGN-COV2 dose groups and the placebo group. (Funded by Regeneron Pharmaceuticals and the Biomedical and Advanced Research and Development Authority of the Department of Health and Human Services; ClinicalTrials.gov number, NCT04425629.).

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Figures

Figure 1
Figure 1. Screening, Randomization, and Treatment.
One patient underwent randomization in error, and Regeneron requested that the patient withdraw from the trial. Four patients in the low-dose REGN-COV2 group withdrew consent: one patient could not participate in the follow-up period, one patient could not have blood drawn and an intravenous line placed, and two patients withdrew consent with no additional information available. Three patients in the high-dose REGN-COV2 group withdrew consent: one patient could not participate in the follow-up period, one patient could not have blood drawn and an intravenous line placed, and one withdrew consent with no additional information available.
Figure 2
Figure 2. SARS-CoV-2 Viral Load over Time.
Shown is the change in mean viral load (in log10 copies per milliliter) from baseline at each visit through day 7 in the overall population (modified full analysis set, which excluded patients who tested negative for severe acute respiratory syndrome coronavirus 2 [SARS-CoV-2] by qualitative reverse-transcriptase polymerase chain reaction at baseline) and in groups defined according to baseline antibody status and baseline viral load. 𝙸 bars in Panel C indicate the standard error. The least-squares mean difference between the groups in the time-weighted average change in viral load (TWA LS mean) from baseline through day 7, expressed as log10 copies per milliliter, was based on analysis-of-covariance models with treatment group, risk factor, and baseline antibody status as fixed effects and baseline viral load and treatment group–by–baseline viral load as covariates. The lower limit of detection (dashed line) is 714 copies per milliliter (2.85 log10 copies per milliliter).
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