N Engl J Med . REGN-COV2, a Neutralizing Antibody Cocktail, in Outpatients with Covid-19

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N Engl J Med


. 2020 Dec 17.
doi: 10.1056/NEJMoa2035002. Online ahead of print.
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



Affiliations

• PMID: 33332778
• DOI: 10.1056/NEJMoa2035002

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 from baseline in viral load from 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.).