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RECOVERY trial: Monoclonal antibody treatment saves lives of seronegative hospitalised COVID-19 patients

The NIHR-supported RECOVERY trial has found that a new monoclonal antibody combination can help save lives of hospitalised patients with severe COVID-19 who were unable to generate an antibody response of their own before beginning treatment.

The investigational treatment called REGEN-COV - a combination of two antiviral monoclonal antibodies - reduced the risk of death and the length of hospital stay for seronegative hospitalised patients with severe COVID-19 (patients who had not mounted their own immune response).

Developed by biotechnology company Regeneron, the antibody treatment works by binding to two different sites on the coronavirus spike protein, neutralising the ability of the virus to infect cells.

The trial assessed the treatment amongst 9,785 hospitalised patients with COVID-19. Participants were randomly allocated to receive usual care plus the antibody combination treatment, or usual care alone. Out of this cohort, at baseline, approximately one-third were seronegative (they had not mounted a natural antibody response of their own), one-half were seropositive (they had already developed natural antibodies), while the serostatus (antibody status) of one-sixth of this group was unknown.

Among patients who had not mounted a natural antibody response of their own on beginning treatment (seronegative), the antibody combination significantly reduced the primary outcome of 28-day mortality by one-fifth compared with usual care alone (24% of patients in the antibody combination group died vs 30% of patients in the usual care group). These results mean that for every 100 such patients treated with this treatment, six lives would be saved.

The antibody treatment also reduced the length of hospital stay for patients in the seronegative group by an average of 4 days from those in the usual care group (median 13 days vs. 17 days). For seronegative patients who were not already on mechanical ventilation at baseline, the antibody treatment also reduced the risk of their health deteriorating to require invasive ventilation, or their risk of dying. These benefits were only found in the seronegative group at baseline.

The study found that the effect of this monoclonal antibody treatment differed between the patients in the seronegative and seropositive patients. There was no overall significant effect on 28-day mortality when assessing the combined data from the seropositive group and the unknown serostatus group, with the seronegative group (overall 20% of patients in the antibody combination group died vs 21% of patients in the usual care group).

Peter Horby, Professor of Emerging Infectious Diseases in the Nuffield Department of Medicine, University of Oxford, and Joint Chief Investigator for the RECOVERY trial, said:

“These results are very exciting. The hope was that by giving a combination of antibodies targeting the SARS-CoV-2 virus we would be able to reduce the worst manifestations of COVID-19. There was, however, great uncertainty about the value of antiviral therapies in late-stage COVID-19 disease. It is wonderful to learn that even in advanced COVID-19 disease, targeting the virus can reduce mortality in patients who have failed to mount an antibody response of their own.”

Professor Nick Lemoine, Medical Director at the NIHR Clinical Research Network said:

"It is fantastic news that the RECOVERY trial has provided evidence to establish another life saving treatment against COVID-19 with this monoclonal antibody combination. The incredible impact the trial continues to have is testament to the scientists, healthcare professionals - but equally the tens of thousands of patients who have taken part. We sincerely want to thank every single one of them for their contribution."

Professor Fiona Watt, Executive Chair, Medical Research Council, said:

“The flagship RECOVERY trial once again leads the way in showing the importance of well-designed clinical trials to identify life-saving treatments. This very important finding means, for patients hospitalised with COVID-19 who do not make their own antibodies to the virus, being treated with antibody-based drugs to the spike protein can reduce their risk of death and time spent in hospital. Patients who have made their own antibodies to the virus do not benefit from the new treatment, which is also important information given the cost of drugs.”

RECOVERY is jointly funded by NIHR and UKRI, while recruitment of participants is supported by the NIHR Clinical Research Network and devolved administrations across the United Kingdom. Since the trial launched in March 2020, the NIHR has helped in the region of 40,000 people take part in this key study - which has produced evidence to establish some of the world’s first identified life saving treatments for COVID-19 - dexamethasone and tocilizumab.

The preliminary results of this evaluation of the monoclonal antibody combination will be available as a pre-print on medRxiv on 16 June 2021 and submitted to a peer-reviewed medical journal.