Early Treatment for Covid-19 with SARS-CoV-2 Neutralizing Antibody Sotrovimab

Abstract

Background: Coronavirus disease 2019 disproportionately results in hospitalization and death in older patients and those with underlying comorbidities. Sotrovimab is a pansarbecovirus monoclonal antibody designed to treat such high-risk patients early in the course of disease, thereby preventing Covid-19 progression. Methods:In this ongoing, multicenter, double-blind, phase 3 trial, nonhospitalized patients with symptomatic Covid-19 and at least one risk factor for disease progression were randomized (1:1) to an intravenous infusion of sotrovimab 500 mg or placebo. The primary efficacy endpoint was the proportion of patients with Covid-19 progression, defined as hospitalization longer than 24 hours or death, through day 29.Results: In this preplanned interim analysis, which included an intent-to-treat population of 583 patients (sotrovimab, 291; placebo, 292), the primary efficacy endpoint was met. The risk of Covid-19 progression was significantly reduced by 85% (97.24% confidence interval, 44% to 96%; P = 0.002) with a total of three (1%) patients progressing to the primary endpoint in the sotrovimab group versus 21 (7%) patients in the placebo group. All five patients admitted to intensive care, including one who died by day 29, received placebo. Safety was assessed in 868 patients (sotrovimab, 430; placebo, 438). Adverse events were reported by 17% and 19% of patients receiving sotrovimab and placebo, respectively; serious adverse events were less common with sotrovimab (2%) versus placebo (6%). Conclusion:Sotrovimab reduced progression of Covid-19 in patients with mild/moderate disease, was well tolerated, and no safety signals were identified..

The use of neutralizing monoclonal antibodies and risk of hospital admission and mortality in patients with COVID-19: a systematic review and meta-analysis of randomized trials

“…After screening, nine randomized controlled trials [ 13–21 ] were included ( Figure 1 ), with a total of 9565 patients who were randomized to the intervention arm and received a neutralizing monoclonal antibody and 7749 patients who were randomized to the control arm and did not receive a neutralizing monoclonal antibody. Five of the included trials [ 15 , 17–20 ] assessed mortality outcomes (with non-zero mortality events), while seven of the included trials [ 13–17 , 20 , 21 ] assessed outcomes on hospital admission. Four of the included trials [ 15–18 ] were performed in multiple countries, whereas the remaining five randomized trials were originated from the United States ( n = 3) [ 13 , 14 , 20 ], the United Kingdom [ 19 ], and Korea [ 21 ], respectively.…”

“…[ 19 ] respectively, REGEN-COV (​casirivimab and imdevimab) was administered as single intravenous/subcutaneous infusion at doses of either 1200 mg, 2400 mg, or 8000 mg in the former two trials [ 15 , 16 ] and at a dose of 8000 mg in the latter trial [ 19 ]; in the trial by Gupta et al. [ 17 ], sotrovimab was administered as single intravenous infusion at a dose of 500 mg; and in the trial by Eom et al. [ 21 ], CT-P59 was administered as single intravenous infusion at doses of either 40 mg/kg or 80 mg/kg.…”

“…The meta-analysis of five trials [ 15 , 17–20 ] revealed no statistically significant difference in the odds of mortality with the administration of a neutralizing monoclonal antibody among patients with COVID-19 relative to non-administration of a neutralizing monoclonal antibody; the estimated effect though indicated mortality benefits ( Figure 2 ; pooled odds ratio = 0.69; 95% confidence interval 0.33–1.47), but is without adequate evidence to refute the null hypothesis of ‘no significant difference’, at the current sample size. On the other hand, the meta-analysis of seven trials [ 13–17 , 20 , 21 ] revealed a statistically significant reduction in the odds of hospital admission with the administration of a neutralizing monoclonal antibody among outpatients with COVID-19 relative to non-administration of a neutralizing monoclonal antibody; the estimated effect indicated reduction in hospital admission ( Figure 3 ; pooled odds ratio = 0.29; 95% confidence interval 0.21–0.42), and with adequate evidence to refute the null hypothesis of ‘no significant difference’, at the current sample size.…”

“…In the trial by Gupta et al. [ 17 ], one patient receiving sotrovimab had an infusion-related reaction (moderate dyspnea) that was considered related to study treatment. In the trial by Gottlieb et al.…”

“…We have pooled the data from studies using different neutralizing monoclonal antibodies formulations, but all of them target SARS-CoV-2. However, all but one included trial [ 13–15 , 17 ] individually observed a significant reduction in hospital admission with the administration of neutralizing monoclonal antibodies among outpatients with COVID-19 relative to non-administration of neutralizing monoclonal antibodies.…”