Safety and Pharmacokinetics of the Anti-SARS-CoV-2 Monoclonal Antibody, Sotrovimab, Administered by Intravenous Injection in Japanese and Caucasian Healthy Volunteers

Background: Sotrovimab is a human monoclonal antibody that targets a domain of the novel coronavirus (SARS-CoV-2) spike protein distinct from the ACE2 receptor binding site. In an overseas phase III study (COMET-ICE) in adult patients with mild to moderate coronavirus disease 2019 (COVID-19) at high risk for disease progression, treatment with sotrovimab (a single 500 mg intravenous (IV) dose) reduced the risk of hospitalization >24 hours and death by 79% compared with placebo, and the drug was well tolerated. In Japan, a special approval granted in September 2021 allows the use of IV sotrovimab in patients with SARS-CoV-2 infection who have risk factors for severe COVID-19 and do not require oxygen administration.Objective: The present study was designed to evaluate whether ethnic-dependent differences in drug exposure and safety exist between healthy adult Japanese and Caucasian populations after receiving 500 mg IV sotrovimab.Methods: we evaluated the safety, tolerability, and pharmacokinetics of a single 500 mg IV dose of sotrovimab in healthy Japanese and Caucasian subjects. Subjects were randomized in a 4: 1 ratio to receive a single, 500 mg IV infusion of sotrovimab or volume-matched saline placebo. The primary endpoints were the safety and pharmacokinetics of sotrovimab up to 29 days post-dosing.Results/Conclusion: When a single 500 mg IV dose of sotrovimab was administered to healthy subjects, no serious adverse events were reported in any subject, and sotrovimab was similarly well-tolerated in both ethnic groups. There was no apparent effect of ethnicity on the pharmacokinetic exposure of sotrovimab. The results support the approved dose and route of administration (a single 500 mg intravenous dose) in Japan.