Effect of the Neutralizing SARS-CoV-2 Antibody Sotrovimab in Preventing Progression of COVID-19: A Randomized Clinical Trial

Abstract

ImportanceOlder patients and those with underlying comorbidities infected with SARS-CoV-2 may be at increased risk of hospitalization and death from COVID-19. Sotrovimab is a neutralizing antibody designed for treatment of high-risk patients to prevent COVID-19 progression.ObjectiveTo evaluate the efficacy and safety of sotrovimab in preventing progression of mild to moderate COVID-19 to severe disease.DesignRandomized, double-blind, multicenter, placebo-controlled, phase 3 study.Setting57 centers in 5 countries.ParticipantsNonhospitalized patients with symptomatic, mild to moderate COVID-19 and at least 1 risk factor for disease progression.InterventionPatients were randomized (1:1) to an intravenous infusion of sotrovimab 500 mg or placebo.Main Outcomes and MeasuresThe primary efficacy outcome was the proportion of patients with COVID-19 progression, defined as all-cause hospitalization longer than 24 hours for acute illness management or death through day 29. Key secondary outcomes included the proportion of patients with COVID-19 progression, defined as emergency room visit, hospitalization of any duration, or death, and proportion of patients developing severe/critical respiratory COVID-19 requiring supplemental oxygen.ResultsAmong 1057 patients randomized (sotrovimab, 528; placebo, 529), all-cause hospitalization longer than 24 hours or death was significantly reduced with sotrovimab (6/528 [1%]) vs placebo (30/529 [6%]) by 79% (95% CI, 50% to 91%; P<.001). Secondary outcome results further demonstrated the effect of sotrovimab in reducing emergency room visits, hospitalization of any duration, or death, which was reduced by 66% (95% CI, 37% to 81%; P<.001), and severe/critical respiratory COVID-19, which was reduced by 74% (95% CI, 41% to 88%; P=.002). No patients receiving sotrovimab required high-flow oxygen, oxygen via nonrebreather mask, or mechanical ventilation compared with 14 patients receiving placebo. The proportion of patients reporting adverse events was similar between treatment groups; sotrovimab was well tolerated, and no safety concerns were identified.Conclusions and RelevanceAmong nonhospitalized patients with mild to moderate COVID-19, a single 500-mg intravenous dose of sotrovimab prevented progression of COVID-19, with a reduction in hospitalization and need for supplemental oxygen. Sotrovimab is a well-tolerated, effective treatment option for patients at high risk for severe morbidity and mortality from COVID-19.Trial RegistrationClinicalTrials.gov Identifier: NCT04545060

Sotrovimab: First Approval

“…Sotrovimab reduced the risk of disease progression in non-hospitalized adults with symptomatic, mild to moderate COVID-19 who are at high risk of progressing to severe disease in a multicenter, double-blind, placebo-controlled phase II/III COMET-ICE trial (NCT04545060) [ 37 , 38 ]. Enrolled patients were aged ≥ 18 years, had tested positive for SARS-CoV-2 infection, confirmed by reverse transcriptase polymerase chain reaction (RT-PCR) or antigen test, and had symptom onset within 5 days prior to randomization.…”

“…Patients were also required to have ≥ 1 of the risk factors: aged ≥ 55 years, diabetes, obesity (body mass index > 30 kg/m 2 ), chronic kidney disease (estimated glomerular filtration rate < 60 mL/min/1.73 m 2 ), congestive heart failure (New York Heart Association class II–IV), chronic obstructive pulmonary disease or moderate to severe asthma. Patients with severe COVID-19 symptoms (shortness of breath at rest, < 94% oxygen saturation or requiring supplemental oxygen) were among those excluded [ 37 , 38 ].…”

“…Patients were randomized to a single dose of sotrovimab 500 mg ( n = 528) or placebo ( n = 529), administered as a 1 h IV infusion [ 37 , 38 ]. Randomization was stratified by age, duration of COVID-19 symptoms and region.…”

“…In the intent-to-treat population, the most common pre-defined risk factors were obesity (63%), followed by aged ≥ 55 years (47%), diabetes (22%) and moderate to severe asthma (17%). Treatment was administered within 3 days or 4–5 days of COVID-19 symptom onset in 59% and 41% of patients, respectively [ 37 , 38 ].…”

Antibody therapies for treatment of non-severe COVID-19

“…Emerging research on the Omicron variant has demonstrated resistance to many mABs discussed in this article. Sotrovimab is the only mAB to demonstrate a significant decrease in all-cause hospitalization in populations infected with the Omicron variant [ 4 ]. We wonder if mABs will prove effective in treating this subset of non-severe COVID-19 infections.…”