Sotrovimab versus usual care in patients admitted to hospital with COVID-19: a randomised, controlled, open-label, platform trial (RECOVERY)
Horby PW., Emberson JR., Peto L., Staplin N., Campbell M., Pessoa-Amorim G., Stewart R., Ghosh D., Cooke G., Blencowe N., Moreno-Cuesta J., Desai P., Hine P., Underwood J., Easom N., Majumdar J., Bhagani S., Baillie JK., Buch MH., Faust SN., Jaki T., Jeffery K., Juszczak E., Knight M., Lim WS., Montgomery A., Mukherjee A., Mumford A., Rowan K., Thwaites G., Mafham M., Haynes R., Landray MJ.
Background: Sotrovimab is a neutralising monoclonal antibody targeting the SARS-COV-2 spike protein that was evaluated in the RECOVERY trial, a randomised, controlled, open-label, platform trial testing treatments for COVID-19. Methods: Patients hospitalised with COVID-19 pneumonia from 107 UK hospitals were randomly allocated to either usual care alone or usual care plus a single 1g infusion of sotrovimab, using web-based unstratified randomisation. Participants were retrospectively categorised as ‘high-antigen’ (the prespecified primary analysis population) if baseline serum SARS-CoV-2 nucleocapsid antigen was above the median concentration, and otherwise as ‘low-antigen’. The primary outcome was 28-day mortality assessed by intention to treat. Recruitment closed on 31 March 2024 when funding ended. ISRCTN (50189673) and clinicaltrials.gov (NCT04381936). Findings: From 4 January 2022 to 19 March 2024, 1723 patients were recruited, 828 allocated sotrovimab and 895 allocated usual care. 720 (42%) were classified as high-antigen, 717 (42%) as low-antigen, and 286 (17%) had unknown antigen status. 1389 (81%) patients were vaccinated, 1179/1438 with known serostatus (82%) had anti-spike antibodies at randomisation, and almost all were infected with Omicron variants. Among high-antigen patients, 82/355 (23%) allocated sotrovimab versus 106/365 (29%) allocated usual care died within 28 days (rate ratio 0.75; 95% CI 0.56-0.99; p=0.046). In an analysis of all randomised patients (regardless of antigen status), 177/828 (21%) allocated sotrovimab versus 201/895 (22%) allocated usual care died within 28 days (rate ratio 0.95; 95% CI 0.77-1.16; p=0.60). Interpretation: In patients hospitalised with COVID-19, sotrovimab was associated with reduced mortality in the primary analysis population who had a high serum SARS-CoV-2 antigen concentration at baseline, but not in the overall population. Treatment options for hospitalised patients are limited, and mortality in those receiving current standard care was high. The emergence of high-level resistance to sotrovimab among subsequent SARS-CoV-2 variants limits its current usefulness, but these results indicate that targeted neutralising antibody therapy could potentially still benefit high-risk hospitalised patients in an era of widespread vaccination and Omicron infection.