The European Commission (EC) has approved the use of Regeron Pharmaceuticals’ casirivimab and imdevimab antibody cocktail, known as REGEN-COV in the US and Ronapreve in the European Union (and other countries) for people aged 12 and older, and for non-hospitalised patients (outpatients) with confirmed COVID-19 who don’t need oxygen supplementation and are at increased risk of progressing to severe COVID-19, and to prevent COVID-19.
Regeron said a single dose reduced the risk of contracting COVID-19 by 81,6% in a late-stage trial, in the two to eight months after the drug's administration.
Data showed the cocktail has the potential to provide long-lasting immunity from COVID-19 infection, said Myron Cohen, who leads monoclonal antibody efforts for the US National Institutes of Health-sponsored COVID Prevention Network, making it particularly helpful for immunocompromised people and those unresponsive to vaccines.
During the eight-month assessment period, there were no hospitalisations for COVID-19 in the REGEN-COV group, but in the placebo group, six such incidents were recorded, Regeneron said.
“This approval adds to the growing number of countries that have recognised our antibody cocktail as an important therapy against COVID-19 to treat non-hospitalised patients already infected with the virus and to prevent infection in the first place," said George D. Yancopoulos, president and Chief Scientific Officer of Regeneron.
“For non-hospitalised infected individuals, our antibody cocktail reduced the risk of hospitalisation or death by 70%; and in the prevention setting it reduced the risk of symptomatic infections by 82%. Further, recently released data not yet reviewed by the EMA suggest a single dose provided long-term protection against COVID-19, beyond the currently authorised once-monthly dosing; we will share these new data with regulatory authorities, including the EMA, to better meet the needs of these patients.”
The EC approval is based on two positive Phase 3 trials involving more than 6,000 individuals that evaluated the efficacy and safety of the antibody cocktail to treat non-hospitalised patients already infected with SARS-CoV-2, and to prevent symptomatic infection in asymptomatic household contacts of SARS-CoV-2 infected individuals (both uninfected and infected contacts).
Regeneron invented the antibody cocktail and is collaborating with Roche, which is primarily responsible for development and distribution outside the US. In addition to this Marketing Authorisation Application, the companies intend to submit a future Type II Variation to the EMA to expand the indication to include the treatment of patients hospitalised because of COVID-19.
In October, the US Food and Drug Administration (FDA) accepted for priority review the first of two Biologics License Applications (BLAs) for REGEN-COV to treat COVID-19 in non-hospitalised patients and as prophylaxis in certain individuals. The second BLA submission will focus on those hospitalised because of COVID-19, and should be completed later this year.
Emergency or temporary pandemic use authorisations are currently in place in more than 40 countries, including the US, India, Switzerland and Canada, and the antibody cocktail is fully approved in Japan and conditionally approved in the United Kingdom and Australia. While REGEN-COV has not been approved by the FDA in the US, it is currently authorised under an Emergency Use Authorization (EUA) for use in certain post-exposure prophylaxis settings and as a treatment for people with mild to moderate COVID-19 who are at high risk of serious consequences from COVID-19.
About the cocktail
REGEN-COV (casirivimab and imdevimab) is a mix of two monoclonal antibodies designed to block infectivity of SARS-CoV-2 using Regeneron’s proprietary VelocImmune and VelociSuite technologies. The two potent, virus-neutralising antibodies that form the cocktail 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 published in the study earlier this year in Cell.
Multiple analyses have shown that the antibody cocktail retains potency against the main variants of concern, including Delta, Beta and Mu. Regeneron will continue actively monitoring the potency of REGEN-COV against emerging variants.
REGEN-COV is not authorised as a substitute for vaccination against COVID-19, or for pre-exposure prophylaxis for prevention of COVID-19, or for use in patients who are in hospital due to COVID-19 or require oxygen therapy, or for people currently using chronic oxygen therapy because of an underlying comorbidity who require an increase in baseline oxygen flow rate due to COVID-19.
Study details
The monoclonal antibody combination REGEN-COV protects against SARS-CoV-2 mutational escape in preclinical and human studies
Richard Copin, Alina Baum, Elzbieta Wloga, Kristen E. Pascal, Stephanie Giordano, Benjamin O. Fulton, Anbo Zhou, Nicole Negron, Kathryn Lanza, Newton Chan, Angel Coppola, Joyce Chiu, Min Ni, Yi Wei, Gurinder S. Atwal, Annabel Romero Hernandez, Kei Saotome, Yi Zhou, Matthew C. Franklin, Andrea T. Hooper, Shane McCarthy, Sara Hamon, Jennifer D. Hamilton, Hilary M. Staples, Kendra Alfson, Ricardo Carrion Jr., Shazia Ali, Thomas Norton, Selin Somersan-Karakaya, Sumathi Sivapalasingam, Gary A. Herman, David M. Weinreich, Leah Lipsich, Neil Stahl, Andrew J. Murphy, George D. Yancopoulos, Christos A. Kyratsous
Published in Cell on 5 June 2021
Highlights
• REGEN-COV retains neutralisation potency against current variants of concern/interest
• In vitro escape studies can predict emergence of viral variants in animals and humans
• Three noncompeting mAb in combination reduce variant risk compared to a combination of two
• Treatment with REGEN-COV in humans does not lead to emergence of viral variants
Summary
Monoclonal antibodies against SARS-CoV-2 are a clinically validated therapeutic option against COVID-19. Because rapidly emerging virus mutants are becoming the next major concern in the fight against the global pandemic, it is imperative that these therapeutic treatments provide coverage against circulating variants and do not contribute to development of treatment-induced emergent resistance.
To this end, we investigated the sequence diversity of the spike protein and monitored emergence of virus variants in SARS-COV-2 isolates found in COVID-19 patients treated with the two-antibody combination REGEN-COV, as well as in preclinical in vitro studies using single, dual, or triple antibody combinations, and in hamster in vivo studies using REGEN-COV or single monoclonal antibody treatments.
Our study demonstrates that the combination of non-competing antibodies in REGEN-COV provides protection against all current SARS-CoV-2 variants of concern/interest and also protects against emergence of new variants and their potential seeding into the population in a clinical setting.
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