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