The prominent global RECOVERY (Randomized Evaluation of COVid-19 thERapY) is one of the world’s largest randomized clinical trials of potential COVID-19 treatments. It was this study that discovered the benefit of dexamethasone in severe COVID-19 cases. The University of Oxford led clinical trial now embraces Regeneron’s monoclonal antibody combination cocktail called REGN-COV2; does the monoclonal antibody cocktail reduce mortality, hospital stay and the need for ventilation?
REGN-COV2 Move to UK
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.
TrialSite has written extensively on this advanced monoclonal antibody combination product. See the link for details.
The Phase 3 open-label trial in patients hospitalized with COVID-19 will compare the effects of adding REGN-COV2 to the usual standard-of-care versus standard-of-care on its own.
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 randomization. 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.
Principal Investigator Point of View
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 randomized clinical trial; this is the only way to be certain about whether it works as a treatment for COVID-19.”
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 randomized 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 hospitalized patients.
“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,” said George D. Yancopoulos, M.D., Ph.D., President and Chief Scientific Officer of Regeneron. “REGN-COV2 was specifically designed by Regeneron scientists to target the virus that causes COVID-19. RECOVERY will be the fourth late-stage randomized clinical trial evaluating REGN-COV2 and will add to our knowledge about how this novel antibody cocktail may help hospitalized patients in need.”
About the Trial
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.
The inclusion of convalescent plasma in the RECOVERY trial was announced in June. The trial will compare adding convalescent plasma (plasma taken from patients who have recovered from COVID-19) to usual standard-of-care versus standard-of-care on its own.
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. Note TrialSite has covered that this IDMC accelerated the greenlight to commence from Phase 1 while the data was still blinded (e.g. sponsor Regeneron wasn’t able to see the underlying data). This was reported directly from Regeneron to TrialSite.
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 under OT number: HHSO100201700020C. 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.
Regeneron (NASDAQ: REGN) is a leading biotechnology company that invents life-transforming medicines for people with serious diseases. Founded and led for over 30 years by physician-scientists, our unique ability to repeatedly and consistently translate science into medicine has led to seven FDA-approved treatments and numerous product candidates in development, all of which were homegrown in our laboratories. Our medicines and pipeline are designed to help patients with eye diseases, allergic and inflammatory diseases, cancer, cardiovascular and metabolic diseases, pain, infectious diseases and rare diseases.
Regeneron is accelerating and improving the traditional drug development process through our proprietary VelociSuite technologies, such as VelocImmune®, which uses unique genetically-humanized mice to produce optimized fully-human antibodies and bispecific antibodies, and through ambitious research initiatives such as the Regeneron Genetics Center, which is conducting one of the largest genetics sequencing efforts in the world.
Call to Action: TrialSite has a keen interest in monitoring REGN-COV2 as it truly came to research via a fairly unorthodox manner—it involved a so-called sentinel population in an early stage Phase 1 clincial trial. Interested in TrialSite’s update and point of view? Sign up for the daily newsletter.