tetano
Editor, Senior Moderator
N Engl J Med
. 2021 Sep 29.
doi: 10.1056/NEJMoa2108163. Online ahead of print.
REGEN-COV Antibody Combination and Outcomes 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], Jing Xiao[SUP] 1 [/SUP], Andrea T Hooper[SUP] 1 [/SUP], Jennifer D Hamilton[SUP] 1 [/SUP], Bret J Musser[SUP] 1 [/SUP], Diana Rofail[SUP] 1 [/SUP], Mohamed Hussein[SUP] 1 [/SUP], Joseph Im[SUP] 1 [/SUP], Dominique Y Atmodjo[SUP] 1 [/SUP], Christina Perry[SUP] 1 [/SUP], Cynthia Pan[SUP] 1 [/SUP], Adnan Mahmood[SUP] 1 [/SUP], Romana Hosain[SUP] 1 [/SUP], John D Davis[SUP] 1 [/SUP], Kenneth C Turner[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], Lilia Roque-Guerrero[SUP] 1 [/SUP], Gerard Acloque[SUP] 1 [/SUP], Hessam Aazami[SUP] 1 [/SUP], Kevin Cannon[SUP] 1 [/SUP], J Abraham Simón-Campos[SUP] 1 [/SUP], Joseph A Bocchini[SUP] 1 [/SUP], Bari Kowal[SUP] 1 [/SUP], A Thomas DiCioccio[SUP] 1 [/SUP], Yuhwen Soo[SUP] 1 [/SUP], Gregory P Geba[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: 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 log[SUB]10[/SUB] copies per milliliter (95% confidence interval [CI], -0.90 to -0.53) in the 1200-mg group and -0.86 log[SUB]10[/SUB] 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.).
. 2021 Sep 29.
doi: 10.1056/NEJMoa2108163. Online ahead of print.
REGEN-COV Antibody Combination and Outcomes 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], Jing Xiao[SUP] 1 [/SUP], Andrea T Hooper[SUP] 1 [/SUP], Jennifer D Hamilton[SUP] 1 [/SUP], Bret J Musser[SUP] 1 [/SUP], Diana Rofail[SUP] 1 [/SUP], Mohamed Hussein[SUP] 1 [/SUP], Joseph Im[SUP] 1 [/SUP], Dominique Y Atmodjo[SUP] 1 [/SUP], Christina Perry[SUP] 1 [/SUP], Cynthia Pan[SUP] 1 [/SUP], Adnan Mahmood[SUP] 1 [/SUP], Romana Hosain[SUP] 1 [/SUP], John D Davis[SUP] 1 [/SUP], Kenneth C Turner[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], Lilia Roque-Guerrero[SUP] 1 [/SUP], Gerard Acloque[SUP] 1 [/SUP], Hessam Aazami[SUP] 1 [/SUP], Kevin Cannon[SUP] 1 [/SUP], J Abraham Simón-Campos[SUP] 1 [/SUP], Joseph A Bocchini[SUP] 1 [/SUP], Bari Kowal[SUP] 1 [/SUP], A Thomas DiCioccio[SUP] 1 [/SUP], Yuhwen Soo[SUP] 1 [/SUP], Gregory P Geba[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: 34587383
- DOI: 10.1056/NEJMoa2108163
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 log[SUB]10[/SUB] copies per milliliter (95% confidence interval [CI], -0.90 to -0.53) in the 1200-mg group and -0.86 log[SUB]10[/SUB] 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.).