REGEN-COV Antibody Combination and Outcomes in Outpatients with Covid-19

Weinreich, David M.; Sivapalasingam, Sumathi; Norton, Thomas; Ali, Shazia; Gao, Haitao; Bhore, Rafia; Xiao, Jing; Hooper, Andrea T.; Hamilton, Jennifer D.; Musser, Bret J.; Rofail, Diana; Hussein, Mohamed; Im, Joseph; Atmodjo, Dominique Y.; Perry, Christina; Pan, Cynthia; Mahmood, Adnan; Hosain, Romana; Davis, John D.; Turner, Kenneth C.; Baum, Alina; Kyratsous, Christos A.; Kim, Yunji; Cook, Amanda; Kampman, Wendy; Roque-Guerrero, Lilia; Acloque, Gerard; Aazami, Hessam; Cannon, Kevin; Simón-Campos, J. Abraham; Bocchini, Joseph A.; Kowal, Bari; DiCioccio, A. Thomas; Soo, Yuhwen; Geba, Gregory P.; Stahl, Neil; Lipsich, Leah; Braunstein, Ned; Herman, Gary; Yancopoulos, George D.

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(10) copies per milliliter (95% confidence interval [CI], −0.90 to −0.53) in the 1200-mg group and −0.86 log(10) 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.)