One of the world’s largest efforts to find effective COVID-19 treatments will evaluate the impact of an ‘antibody cocktail’, REGN-COV2, on hospital stays, death rates and the need for ventilation in seriously ill patients..
The University of Oxford and its partner Regeneron Pharmaceuticals, Inc. today announced that RECOVERY (Randomised Evaluation of COVid-19 thERapY), one of the world’s largest randomised clinical trials of potential COVID-19 treatments, will evaluate Regeneron’s investigational anti-viral antibody cocktail, REGN-COV2.
The Phase 3 open-label trial in patients hospitalised with COVID-19 will compare the effects of adding REGN-COV2 to the usual methods of care compared to these basic methods alone.
Professor Fiona Watt, Executive Chair of the Medical Research Council, part of UK Research and Innovation (UKRI), said: “With our support, the RECOVERY trial has previously found the most clinically effective treatment for COVID-19 so far, dexamethasone.
“The same UK-wide trial will now test a new treatment designed specifically to combat the virus that causes the disease. Monoclonal, or targeted, antibodies are already used to treat cancer and autoimmune diseases. The new trial will tell us whether antibodies that attack the virus can be an effective treatment for Covid-19.”
Peter Horby, Professor of Emerging Infectious Diseases and Global Health, Nuffield Department of Medicine, University of Oxford and chief investigator of the trial, said: “We have already discovered that one treatment, dexamethasone, benefits COVID-19 patients, but the death rate remains too high so we must keep searching for others. The RECOVERY trial was specifically designed so that when promising investigational drugs such as REGN-COV2 became available they can be tested quickly.
“We are looking forward to seeing whether REGN-COV2 is safe and effective in the context of a large-scale randomised clinical trial; this is the only way to be certain about whether it works as a treatment for COVID-19.”
Deputy Chief Medical Officer Professor Jonathan Van-Tam said: “Funded by the UK National Institute for Health Research (NIHR) and UK Research and Innovation (UKRI), RECOVERY is globally recognised as the largest and the most successful COVID-19 platform trial to date. Today’s news is another promising step in the search to find effective treatments, which will improve our ability to deal with this destructive virus, and a testament to the confidence that others around the world have in this brilliantly conceived and executed trial.
“We’ve had some crucial results from RECOVERY so far, including the life-saving treatment dexamethasone and, as importantly, confirmation that other drugs do not work. I look forward to seeing how REGN-COV2 performs in clinical trials, and I urge people to volunteer in this research which could ultimately save many lives.”
See also: NHS Contract Tracing App Relaunched as Human Challenge Trials Planned
George D. Yancopoulos, M.D., Ph.D., President and Chief Scientific Officer of Regeneron, said, “The world urgently needs new medicines to combat COVID-19, and well-designed trials to evaluate new treatment options will quickly help us learn which are most effective.
“REGN-COV2 was specifically designed by Regeneron scientists to target the virus that causes COVID-19. RECOVERY will be the fourth late-stage randomised clinical trial evaluating REGN-COV2 and will add to our knowledge about how this novel antibody cocktail may help hospitalised patients in need.”
REGN-COV2 is the first specifically designed COVID-19 therapy being evaluated by RECOVERY. It was selected, in part, based on its emerging safety profile in humans, pre-clinical data showing it could protect against viral escape mutations, and prevention and treatment studies in non-human primates showing it reduced the amount of virus and associated damage in the lungs.
REGN-COV2 is currently being studied in two Phase 2/3 clinical trials for the treatment of COVID-19 and in a Phase 3 trial for the prevention of COVID-19 in household contacts of infected individuals.
Martin Landray, Professor of Medicine & Epidemiology, Nuffield Department of Population Health, University of Oxford, added, “Throughout the COVID-19 pandemic we have seen the power of randomised trials to provide rigorous assessment of potential treatments. Up to now, we have largely been studying whether existing drugs can be re-purposed to tackle this new disease, but we now have the opportunity to rigorously assess the impact of a drug specifically designed to target this coronavirus.
“There are good reasons to be excited about this new development – RECOVERY will provide a robust assessment of the effect of this lab-manufactured monoclonal antibody combination treatment in hospitalised patients.
“We are very grateful to the patients who have already taken part in the trial and to those who will participate in this next phase of RECOVERY. We would not be able to find the best treatments without their support and that of the thousands of hospital and research staff who are working with us.”
The open-label RECOVERY trial will assess the impact of adding REGN-COV2 to the usual standard-of-care on all-cause mortality 28 days after randomisation. Other endpoints include the impact on hospital stay and the need for ventilation. It is anticipated that at least 2,000 patients will be randomly allocated to receive REGN-COV2 plus usual standard-of-care, and results will be compared with at least 2,000 patients who receive standard-of-care on its own. Usual standard-of-care varies by local hospital.
The trial is being coordinated by researchers at the University of Oxford, which acts as the sponsor for the research, working with clinical teams at 176 hospital sites across the UK.
The RECOVERY trial is also studying the impact of convalescent plasma (plasma taken from patients who have recovered from COVID-19), tocilizumab (a drug which targets a specific part of the immune system), and azithromycin (usually used as an antibiotic).
The RECOVERY trial is conducted by the registered clinical trials units in the Nuffield Department of Population Health in partnership with the Nuffield Department of Medicine. The trial is supported by a grant to the University of Oxford from UK Research and Innovation/National Institute for Health Research (NIHR) and by core funding provided by NIHR Oxford Biomedical Research Centre, Wellcome, the Bill and Melinda Gates Foundation, the Department for International Development, Health Data Research UK, the Medical Research Council Population Health Research Unit and NIHR Clinical Trials Unit Support Funding.
The trial involves many thousands of doctors, nurses, pharmacists, and research administrators at 176 hospitals across the whole of the UK, supported by staff at the NIHR Clinical Research Network, NHS DigiTrials, Public Health England, Department of Health & Social Care, the Intensive Care National Audit & Research Centre, Public Health Scotland, the Secure Anonymised Information Linkage at University of Swansea, and the NHS in England, Scotland, Wales and Northern Ireland.
REGN-COV2 comprises two monoclonal antibodies (REGN10933 and REGN10987) and was designed specifically by Regeneron scientists to block infectivity of SARS-CoV-2, the virus that causes COVID-19. They evaluated thousands of fully-human antibodies produced by the company’s VelocImmune® mice, which have been genetically modified to have a human immune system, as well as antibodies identified from humans who have recovered from COVID-19.
The two potent, virus-neutralizing antibodies that form REGN-COV2 bind non-competitively to the critical receptor binding domain of the virus’s spike protein, which diminishes the ability of mutant viruses to escape treatment and protects against spike variants that have arisen in the human population, as detailed in Science.
An Independent Data Monitoring Committee is monitoring all Regeneron-led REGN-COV2 Phase 2 and 3 trials, and all trials continue to enroll patients.
REGN-COV2’s development and manufacturing has been funded in part by the Biomedical Advanced Research and Development Authority (BARDA), part of the Office of the Assistant Secretary for Preparedness and Response at the U.S. Department of Health and Human Services. Regeneron has recently partnered with Roche to increase the global supply of REGN-COV2.
If REGN-COV2 proves safe and effective in clinical trials and regulatory approvals are granted, Regeneron will manufacture and distribute it in the U.S. and Roche will develop, manufacture and distribute it outside the U.S.