Early Treatment for Covid-19 with SARS-CoV-2 Neutralizing Antibody Sotrovimab
Interim results from the COMET-ICE trial showing significantly lower hospitalization with treatment. NCT04545060 (history)
.Efficacy is variant dependent. In Vitro studies predict lower efficacy for BA.1 [Liu, Sheward, VanBlargan] and a lack of efficacy for BA.2 [Zhou]. US EUA has been revoked.
risk of death, 66.6% lower, RR 0.33, p = 1.00, treatment 0 of 291 (0.0%), control 1 of 292 (0.3%), NNT 292, relative risk is not 0 because of continuity correction due to zero events (with reciprocal of the contrasting arm).
risk of mechanical ventilation, 80.0% lower, RR 0.20, p = 0.50, treatment 0 of 291 (0.0%), control 2 of 292 (0.7%), NNT 146, relative risk is not 0 because of continuity correction due to zero events (with reciprocal of the contrasting arm).
risk of ICU admission, 90.9% lower, RR 0.09, p = 0.06, treatment 0 of 291 (0.0%), control 5 of 292 (1.7%), NNT 58, relative risk is not 0 because of continuity correction due to zero events (with reciprocal of the contrasting arm).
risk of hospitalization, 80.9% lower, RR 0.19, p < 0.001, treatment 4 of 291 (1.4%), control 21 of 292 (7.2%), NNT 17.
risk of hospitalization, 85.7% lower, RR 0.14, p < 0.001, treatment 3 of 291 (1.0%), control 21 of 292 (7.2%), NNT 16, >24hrs, primary outcome.
Effect extraction follows pre-specified rules prioritizing more serious outcomes. Submit updates
Gupta et al., 26 May 2021, Double Blind Randomized Controlled Trial, USA, preprint, 22 authors, trial NCT04545060 (history)
n e w e ng l a n d j o u r na l
m e dic i n e
Early Treatment for Covid-19 with SARS-CoV-2
Neutralizing Antibody Sotrovimab
Anil Gupta, M.D., Yaneicy Gonzalez‑Rojas, M.D., Erick Juarez, M.D.,
Manuel Crespo Casal, M.D., Jaynier Moya, M.D., Diego R. Falci, M.D., Ph.D.,
Elias Sarkis, M.D., Joel Solis, M.D., Hanzhe Zheng, Ph.D., Nicola Scott, M.Sc.,
Andrea L. Cathcart, Ph.D., Christy M. Hebner, Ph.D., Jennifer Sager, Ph.D.,
Erik Mogalian, Pharm.D., Ph.D., Craig Tipple, M.B., B.S., Ph.D.,
Amanda Peppercorn, M.D., Elizabeth Alexander, M.D., Phillip S. Pang, M.D., Ph.D.,
Almena Free, M.D., Cynthia Brinson, M.D., Melissa Aldinger, Pharm.D.,
and Adrienne E. Shapiro, M.D., Ph.D., for the COMET-ICE Investigators*
A BS T R AC T
Coronavirus disease 2019 (Covid-19) disproportionately results in hospitalization
or death in older patients and those with underlying conditions. Sotrovimab is a
pan-sarbecovirus monoclonal antibody that was designed to prevent progression
of Covid-19 in high-risk patients early in the course of disease.
In this ongoing, multicenter, double-blind, phase 3 trial, we randomly assigned,
in a 1:1 ratio, nonhospitalized patients with symptomatic Covid-19 (≤5 days after
the onset of symptoms) and at least one risk factor for disease progression to receive a single infusion of sotrovimab at a dose of 500 mg or placebo. The primary
efficacy outcome was hospitalization (for >24 hours) for any cause or death
within 29 days after randomization.
In this prespecified interim analysis, which included an intention-to-treat population of 583 patients (291 in the sotrovimab group and 292 in the placebo group),
3 patients (1%) in the sotrovimab group, as compared with 21 patients (7%) in the
placebo group, had disease progression leading to hospitalization or death (relative risk reduction, 85%; 97.24% confidence interval, 44 to 96; P = 0.002). In the
placebo group, 5 patients were admitted to the intensive care unit, including 1 who
died by day 29. Safety was assessed in 868 patients (430 in the sotrovimab group
and 438 in the placebo group). Adverse events were reported by 17% of the patients
in the sotrovimab group and 19% of those in the placebo group; serious adverse
events were less common with sotrovimab than with placebo (in 2% and 6% of
the patients, respectively).
Among high-risk patients with mild-to-moderate Covid-19, sotrovimab reduced
the risk of disease progression. No safety signals were identified. (Funded by Vir
Biotechnology and GlaxoSmithKline; COMET-ICE ClinicalTrials.gov number,
From the Albion Finch Medical Centre,
William Osler Health Centre, Toronto
(A.G.); Optimus U (Y.G.-R.) and Florida
International Medical Research (E.J.), Miami, Pines Care Research Center, Pembroke Pines (J.M.), and Sarkis Clinical
Trials, Gainesville (E.S.) — all in Florida;
Álvaro Cunqueiro Hospital, IIS Galicia
Sur, Vigo, Spain (M.C.C.); Hospital de
Clínicas de Porto Alegre, Porto Alegre,
Brazil (D.R.F.); Centex Studies, McAllen
(J. Solis), and Central Texas Clinical Research, Austin (C.B.) — both in Texas; Vir
Biotechnology, San Francisco (H.Z., A.L.C.,
C.M.H., J. Sager, E.M., E.A., P.S.P., M.A.);
GlaxoSmithKline, Stevenage, United Kingdom (N.S., C.T.); GlaxoSmithKline, Cambridge, MA (A.P.); Pinnacle Research
Group, Anniston, AL (A.F.); and the Departments of Global Health and Medicine, University of Washington, and Fred
Hutchinson Cancer Research..
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