TY - JOUR

T1 - A neutralizing monoclonal antibody for hospitalized patients with Covid-19

AU - Lundgren, J. D.

AU - Grund, B.

AU - Barkauskas, C. E.

AU - Holland, T. L.

AU - Gottlieb, R. L.

AU - Sandkovsky, U.

AU - Brown, S. M.

AU - Knowlton, K. U.

AU - Self, W. H.

AU - Files, D. C.

AU - Jain, M. K.

AU - Benfield, T.

AU - Bowdish, M. E.

AU - Leshnower, B. G.

AU - Baker, J. V.

AU - Jensen, J. U.

AU - Gardner, E. M.

AU - Ginde, A. A.

AU - Harris, E. S.

AU - Johansen, I. S.

AU - Markowitz, N.

AU - Matthay, M. A.

AU - Østergaard, L.

AU - Chang, C. C.

AU - Davey, V. J.

AU - Goodman, A.

AU - Higgs, E. S.

AU - Murray, D. D.

AU - Murray, T. A.

AU - Paredes, R.

AU - Parmar, M. K.B.

AU - Phillips, A. N.

AU - Reilly, C.

AU - Sharma, S.

AU - Dewar, R. L.

AU - Teitelbaum, M.

AU - Wentworth, D.

AU - Cao, H.

AU - Klekotka, P.

AU - Babiker, A. G.

AU - Gelijns, A. C.

AU - Kan, V. L.

AU - Polizzotto, M. N.

AU - Thompson, B. T.

AU - Lane, H. C.

AU - Neaton, J. D.

AU - ACTIV-3/TICO LY-CoV555 Study Group

N1 - Publisher Copyright: Copyright © 2020 Massachusetts Medical Society.

PY - 2021/3/11

Y1 - 2021/3/11

N2 - Background: LY-CoV555, a neutralizing monoclonal antibody, has been associated with a decrease in viral load and the frequency of hospitalizations or emergency department visits among outpatients with coronavirus disease 2019 (Covid-19). Data are needed on the effect of this antibody in patients who are hospitalized with Covid-19. Methods: In this platform trial of therapeutic agents, we randomly assigned hospitalized patients who had Covid-19 without end-organ failure in a 1:1 ratio to receive either LY-CoV555 or matching placebo. In addition, all the patients received high-quality supportive care as background therapy, including the antiviral drug remdesivir and, when indicated, supplemental oxygen and glucocorticoids. LY-CoV555 (at a dose of 7000 mg) or placebo was administered as a single intravenous infusion over a 1-hour period. The primary outcome was a sustained recovery during a 90-day period, as assessed in a time-to-event analysis. An interim futility assessment was performed on the basis of a seven-category ordinal scale for pulmonary function on day 5. Results: On October 26, 2020, the data and safety monitoring board recommended stopping enrollment for futility after 314 patients (163 in the LY-CoV555 group and 151 in the placebo group) had undergone randomization and infusion. The median interval since the onset of symptoms was 7 days (interquartile range, 5 to 9). At day 5, a total of 81 patients (50%) in the LY-CoV555 group and 81 (54%) in the placebo group were in one of the two most favorable categories of the pulmonary outcome. Across the seven categories, the odds ratio of being in a more favorable category in the LY-CoV555 group than in the placebo group was 0.85 (95% confidence interval [CI], 0.56 to 1.29; P = 0.45). The percentage of patients with the primary safety outcome (a composite of death, serious adverse events, or clinical grade 3 or 4 adverse events through day 5) was similar in the LY-CoV555 group and the placebo group (19% and 14%, respectively; odds ratio, 1.56; 95% CI, 0.78 to 3.10; P = 0.20). The rate ratio for a sustained recovery was 1.06 (95% CI, 0.77 to 1.47). Conclusions: Monoclonal antibody LY-CoV555, when coadministered with remdesivir, did not demonstrate efficacy among hospitalized patients who had Covid-19 without end-organ failure.

AB - Background: LY-CoV555, a neutralizing monoclonal antibody, has been associated with a decrease in viral load and the frequency of hospitalizations or emergency department visits among outpatients with coronavirus disease 2019 (Covid-19). Data are needed on the effect of this antibody in patients who are hospitalized with Covid-19. Methods: In this platform trial of therapeutic agents, we randomly assigned hospitalized patients who had Covid-19 without end-organ failure in a 1:1 ratio to receive either LY-CoV555 or matching placebo. In addition, all the patients received high-quality supportive care as background therapy, including the antiviral drug remdesivir and, when indicated, supplemental oxygen and glucocorticoids. LY-CoV555 (at a dose of 7000 mg) or placebo was administered as a single intravenous infusion over a 1-hour period. The primary outcome was a sustained recovery during a 90-day period, as assessed in a time-to-event analysis. An interim futility assessment was performed on the basis of a seven-category ordinal scale for pulmonary function on day 5. Results: On October 26, 2020, the data and safety monitoring board recommended stopping enrollment for futility after 314 patients (163 in the LY-CoV555 group and 151 in the placebo group) had undergone randomization and infusion. The median interval since the onset of symptoms was 7 days (interquartile range, 5 to 9). At day 5, a total of 81 patients (50%) in the LY-CoV555 group and 81 (54%) in the placebo group were in one of the two most favorable categories of the pulmonary outcome. Across the seven categories, the odds ratio of being in a more favorable category in the LY-CoV555 group than in the placebo group was 0.85 (95% confidence interval [CI], 0.56 to 1.29; P = 0.45). The percentage of patients with the primary safety outcome (a composite of death, serious adverse events, or clinical grade 3 or 4 adverse events through day 5) was similar in the LY-CoV555 group and the placebo group (19% and 14%, respectively; odds ratio, 1.56; 95% CI, 0.78 to 3.10; P = 0.20). The rate ratio for a sustained recovery was 1.06 (95% CI, 0.77 to 1.47). Conclusions: Monoclonal antibody LY-CoV555, when coadministered with remdesivir, did not demonstrate efficacy among hospitalized patients who had Covid-19 without end-organ failure.

U2 - 10.1056/NEJMoa2033130

DO - 10.1056/NEJMoa2033130

M3 - Journal article

C2 - 33356051

AN - SCOPUS:85099949020

VL - 384

SP - 905

EP - 914

JO - New England Journal of Medicine

JF - New England Journal of Medicine

SN - 0028-4793

IS - 10

ER -