The Randomised Evaluation of COVID-19 Therapy (RECOVERY) trial has found that sotrovimab reduced the risk of death in patients hospitalised with COVID-19, but only in those with higher levels of the virus present in their blood. The results have been published on medRxiv and will be submitted to a peer-reviewed medical journal.
Sotrovimab is an antiviral monoclonal antibody treatment that works by sticking to the surface of the SARS-CoV-2 virus to stop it from replicating. Previous studies have shown that antiviral monoclonal antibody treatments can reduce the risk of hospitalisation and death in patients in the early stages of COVID-19 infection, and in some hospitalised patients without antibodies against the virus. However, these trials were conducted in patients who were mostly unvaccinated, so it was not known which, if any, current patients could benefit from treatment.
1,723 patients from 107 UK hospitals participated in the sotrovimab evaluation between January 2022 and March 2024. Over 80% of the patients were vaccinated and over 80% had COVID-19 antibodies present in their blood. Almost all of the participants were infected with an Omicron variant of COVID-19.
Key findings
- Sotrovimab reduced the risk of death within 28 days of randomisation by 25% in patients with high viral antigen levels, though there was substantial uncertainty about the size of benefit (rate ratio 0.75; 95% confidence interval 0.56 to 0.99, p=0.046); 82/355 (23%) of those allocated sotrovimab died versus 106/365 (29%) of those in the usual care group.
- No benefit was seen when considering all patients together regardless of their blood virus levels (high, low and unknown antigen levels). Among all patients, 177/828 (21%) of those allocated sotrovimab died versus 201/895 (22%) in the usual care group (rate ratio 0.95; 95% confidence interval 0.77 to 1.16; p=0.60).
A major limitation of monoclonal antibody therapies has been the frequent emergence of new variants of the virus that are resistant to treatment. The RECOVERY sotrovimab evaluation was the first directed at patients with the Omicron variant that became dominant in late 2021 and which was resistant to most other monoclonal antibodies in use. Although sotrovimab reduced the risk of death in some patients in RECOVERY, many recent SARS-CoV-2 variants have now developed resistance to sotrovimab, limiting its current effectiveness.
Dr Leon Peto, Senior Clinical Research Fellow at Oxford Population Health, said ‘Our results provide promising evidence that monoclonal antibody therapy could still be effective in patients hospitalised with COVID-19 if it is targeted towards the right people. Severe COVID-19 is much rarer now than during the pandemic, but in RECOVERY those with high levels of virus in their blood still had a nearly one in three risk of death, which was substantially reduced with sotrovimab.
‘However, this is based on a smaller numbers of patients than previous RECOVERY evaluations, so the results should be interpreted with caution. Although these results can inform future development of monoclonal antibody therapy, resistance to sotrovimab has become common in circulating viruses since the study ended, so this particular monoclonal treatment may not be effective in patients currently admitted with COVID-19.’
The RECOVERY trial was supported by grants to the University of Oxford from the National Institute for Health and Care Research, UK Research and Innovation, and Wellcome. The decision to add sotrovimab to the trial was made by the University of Oxford researchers leading the trial and the Trial Steering Committee in conjunction with the Chief Medical Officer, following a recommendation by the UK COVID-19 Therapeutics Advisory Panel.
GSK and Vir Biotechnology, the manufacturers of sotrovimab, supported the study through supply of sotrovimab but did not have any role in the study design, data collection or data analysis. The RECOVERY trial continues to evaluate other treatments for patients hospitalised with influenza or community-acquired pneumonia, funded by Flu Lab.