An Open-Label Phase Ii Trial of Sotrovimab (Vir-7831) Prophylaxis Against Covid-19 Infection in Immunocompromised Individuals with Impaired Sars-Cov-2 Humoral Immunity

BACKGROUND Immunocompromised individuals have a limited humoral immune response to SARS-CoV-2 vaccination and are at higher risk of severe COVID-19. Sotrovimab is a monoclonal antibody (mAb) targeting a conserved SARS-CoV-2 spike protein epitope. METHODS This phase II open-label study evaluated the safety and tolerability of sotrovimab pre-exposure prophylaxis in immunocompromised adults with impaired vaccine response. Participants received sotrovimab 500 mg IV on Treatment Day (TD) 1 and 2000 mg IV on TD2 due to the spread of the Omicron BA.2 subvariant. Follow-up lasted 36 weeks (~5 half-lives), assessing safety and tolerability, PK, COVID-19 incidence and severity, and quality of life.  RESULTS Ninety-three subjects received 500 mg on TD1, of whom 81 received 2000 mg on TD2. Three patients reported five drug-related adverse events, four grade 2 infusion-related reactions and one grade 2 headache, all resolving quickly. Among 35 SARS-CoV-2 cases, 94% had no activity limitations or hospitalizations per the National Institute of Allergy and Infectious Diseases Ordinal Scale. Sotrovimab exhibited dose-dependent increases in exposures at doses of 500 mg and 2000 mg.  CONCLUSION Sotrovimab pre-exposure prophylaxis had a favorable safety profile and was well tolerated at both doses, with low immunogenicity. These findings support mAbs’ safety as COVID-19 pre-exposure prophylaxis in this population.