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

 

David M. Weinreich, M.D., 

Sumathi Sivapalasingam, M.D., 

Thomas Norton, M.D., 

Shazia Ali, Pharm.D., 

Haitao Gao, Ph.D., 

Rafia Bhore, Ph.D., 

Bret J. Musser, Ph.D., 

Yuhwen Soo, Ph.D., 

Diana Rofail, Ph.D., 

Joseph Im, B.S., 

Christina Perry, M.B.A., 

Cynthia Pan, B.Pharm., 

 for the Trial Investigators*

DOI: 10.1056/NEJMoa2035002

PDF: 

https://www.nejm.org/doi/pdf/10.1056/NEJMoa2035002?articleTools=true

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. opens in new tab.)

https://www.nejm.org/doi/full/10.1056/NEJMoa2035002