NEJM - Neutralizing Antibody LY-COV555

The new england journal of medicine Original Article SARS-CoV-2 Neutralizing Antibody LY-CoV555 in Outpatients with Covid-19 Peter Chen, M.D., Ajay Nirula, M.D., Ph.D., Barry Heller, M.D., Robert L. Gottlieb, M.D., Ph.D., Joseph Boscia, M.D., Jason Morris, M.D., Gregory Huhn, M.D., M.P.H.T.M., Jose Cardona, M.D., Bharat Mocherla, M.D., Valentina Stosor, M.D., Imad Shawa, M.D., Andrew C. Adams, Ph.D., Jacob Van Naarden, B.S., Kenneth L. Custer, Ph.D., Lei Shen, Ph.D., Michael Durante, M.S., Gerard Oakley, M.D., Andrew E. Schade, M.D., Ph.D., Janelle Sabo, Pharm.D., Dipak R. Patel, M.D., Ph.D., Paul Klekotka, M.D., Ph.D., and Daniel M. Skovronsky, M.D., Ph.D., for the BLAZE-1 Investigators* ABSTRACT BACKGROUND Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) causes coronavirus From the Department of Medicine, disease 2019 (Covid-19), which is most frequently mild yet can be severe and life- Women’s Guild Lung Institute, Cedars– threatening. Virus-neutralizing monoclonal antibodies are predicted to reduce viral Sinai Medical Center, Los Angeles (P.C.), and Long Beach Clinical Trials, Long load, ameliorate symptoms, and prevent hospitalization. Beach (B.H.) — both in California; Eli Lilly, Indianapolis (A.N., A.C.A., J.V.N., METHODS K.L.C., L.S., M.D., G.O., A.E.S., J.S., In this ongoing phase 2 trial involving outpatients with recently diagnosed mild D.R.P., P.K., D.M.S.), and Franciscan Health, Greenwood (I.S.) — both in Indi- or moderate Covid-19, we randomly assigned 452 patients to receive a single intra- ana; Baylor University Medical Center venous infusion of neutralizing antibody LY-CoV555 in one of three doses (700 mg, and Baylor Scott and White Research In- 2800 mg, or 7000 mg) or placebo and evaluated the quantitative virologic end stitute, Dallas (R.L.G.); Vitalink Research, Union, SC (J.B.); Imperial Health, Lake points and clinical outcomes. The primary outcome was the change from baseline Charles, LA (J.M.); Cook County Health in the viral load at day 11. The results of a preplanned interim analysis as of Sep- (G.H.) and Northwestern University tember 5, 2020, are reported here. Feinberg School of Medicine (V.S.), Chi- cago; Indago Research and Health Cen- ter, Hialeah, FL (J.C.); and Las Vegas RESULTS Medical Research Center, Las Vegas At the time of the interim analysis, the observed mean decrease from baseline in (B.M.). Address reprint requests to Dr. the log viral load for the entire population was −3.81, for an elimination of more Skovronsky at Eli Lilly, 893 Delaware St., than 99.97% of viral RNA. For patients who received the 2800-mg dose of LY- Indianapolis, IN 46225, or at s kovronsky_ daniel@ lilly . com. CoV555, the difference from placebo in the decrease from baseline was −0.53 (95% confidence interval [CI], −0.98 to −0.08; P = 0.02), for a viral load that was lower *A list of the BLAZE-1 investigators is provided in the Supplementary Appen- by a factor of 3.4. Smaller differences from placebo in the change from baseline dix, available at NEJM.org. were observed among the patients who received the 700-mg dose (−0.20; 95% CI, Drs. Chen and Nirula contributed equally −0.66 to 0.25; P = 0.38) or the 7000-mg dose (0.09; 95% CI, −0.37 to 0.55; P = 0.70). to this article. On days 2 to 6, the patients who received LY-CoV555 had a slightly lower severity This article was published on October 28, of symptoms than those who received placebo. The percentage of patients who had 2020, at NEJM.org. a Covid-19–related hospitalization or visit to an emergency department was 1.6% DOI: 10.1056/NEJMoa2029849 in the LY-CoV555 group and 6.3% in the placebo group. Copyright © 2020 Massachusetts Medical Society. CONCLUSIONS In this interim analysis of a phase 2 trial, one of three doses of neutralizing antibody LY-CoV555 appeared to accelerate the natural decline in viral load over time, where- as the other doses had not by day 11. (Funded by Eli Lilly; BLAZE-1 ClinicalTrials.gov number, NCT04427501.) n engl j med nejm.org 1 The New England Journal of Medicine Downloaded from nejm.org on November 19, 2020. For personal use only. No other uses without permission. Copyright © 2020 Massachusetts Medical Society. All rights reserved.