tetano
Editor, Senior Moderator
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[SUP] 1 [/SUP], Sumathi Sivapalasingam[SUP] 1 [/SUP], Thomas Norton[SUP] 1 [/SUP], Shazia Ali[SUP] 1 [/SUP], Haitao Gao[SUP] 1 [/SUP], Rafia Bhore[SUP] 1 [/SUP], Bret J Musser[SUP] 1 [/SUP], Yuhwen Soo[SUP] 1 [/SUP], Diana Rofail[SUP] 1 [/SUP], Joseph Im[SUP] 1 [/SUP], Christina Perry[SUP] 1 [/SUP], Cynthia Pan[SUP] 1 [/SUP], Romana Hosain[SUP] 1 [/SUP], Adnan Mahmood[SUP] 1 [/SUP], John D Davis[SUP] 1 [/SUP], Kenneth C Turner[SUP] 1 [/SUP], Andrea T Hooper[SUP] 1 [/SUP], Jennifer D Hamilton[SUP] 1 [/SUP], Alina Baum[SUP] 1 [/SUP], Christos A Kyratsous[SUP] 1 [/SUP], Yunji Kim[SUP] 1 [/SUP], Amanda Cook[SUP] 1 [/SUP], Wendy Kampman[SUP] 1 [/SUP], Anita Kohli[SUP] 1 [/SUP], Yessica Sachdeva[SUP] 1 [/SUP], Ximena Graber[SUP] 1 [/SUP], Bari Kowal[SUP] 1 [/SUP], Thomas DiCioccio[SUP] 1 [/SUP], Neil Stahl[SUP] 1 [/SUP], Leah Lipsich[SUP] 1 [/SUP], Ned Braunstein[SUP] 1 [/SUP], Gary Herman[SUP] 1 [/SUP], George D Yancopoulos[SUP] 1 [/SUP], Trial Investigators
Affiliations
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 log[SUB]10[/SUB] copies per milliliter (95% confidence interval [CI], -1.02 to -0.11) among patients who were serum antibody-negative at baseline and -0.41 log[SUB]10[/SUB] 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.).
. 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[SUP] 1 [/SUP], Sumathi Sivapalasingam[SUP] 1 [/SUP], Thomas Norton[SUP] 1 [/SUP], Shazia Ali[SUP] 1 [/SUP], Haitao Gao[SUP] 1 [/SUP], Rafia Bhore[SUP] 1 [/SUP], Bret J Musser[SUP] 1 [/SUP], Yuhwen Soo[SUP] 1 [/SUP], Diana Rofail[SUP] 1 [/SUP], Joseph Im[SUP] 1 [/SUP], Christina Perry[SUP] 1 [/SUP], Cynthia Pan[SUP] 1 [/SUP], Romana Hosain[SUP] 1 [/SUP], Adnan Mahmood[SUP] 1 [/SUP], John D Davis[SUP] 1 [/SUP], Kenneth C Turner[SUP] 1 [/SUP], Andrea T Hooper[SUP] 1 [/SUP], Jennifer D Hamilton[SUP] 1 [/SUP], Alina Baum[SUP] 1 [/SUP], Christos A Kyratsous[SUP] 1 [/SUP], Yunji Kim[SUP] 1 [/SUP], Amanda Cook[SUP] 1 [/SUP], Wendy Kampman[SUP] 1 [/SUP], Anita Kohli[SUP] 1 [/SUP], Yessica Sachdeva[SUP] 1 [/SUP], Ximena Graber[SUP] 1 [/SUP], Bari Kowal[SUP] 1 [/SUP], Thomas DiCioccio[SUP] 1 [/SUP], Neil Stahl[SUP] 1 [/SUP], Leah Lipsich[SUP] 1 [/SUP], Ned Braunstein[SUP] 1 [/SUP], Gary Herman[SUP] 1 [/SUP], George D Yancopoulos[SUP] 1 [/SUP], 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 log[SUB]10[/SUB] copies per milliliter (95% confidence interval [CI], -1.02 to -0.11) among patients who were serum antibody-negative at baseline and -0.41 log[SUB]10[/SUB] 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.).