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COVID-19: Early Data Shows Regeneron’s Antibody Cocktail Curbs Virus, Speeds Recovery
By T. Chakraborty, Ph.D. & Judy Ya-Hsuan Lin
A number of pharmaceutical companies are scrambling to develop therapeutics or vaccines to counter the COVID-19 pandemic that has caused over one million deaths and 30 million confirmed cases so far. Recently, several candidates have registered encouraging results from their initial trials, including Regeneron Pharmaceutical Inc’s COVID-19 antibody cocktail (REGN-COV2).
When given to COVID-19 patients who weren’t sick enough to be hospitalized, the antibody cocktail was able to lower the virus levels and relieve symptoms efficiently and quickly. The above-mentioned trial is a subset of a bigger program that consists of studies of the antibody cocktail for the treatment of patients who are hospitalized, and for preventing infection in people exposed to COVID-19.
An elated President and Chief Scientific Officer of Regeneron, George D. Yancopoulos, M.D., Ph.D., commented “After months of incredibly hard work by our talented team, we are extremely gratified to see that Regeneron’s antibody cocktail REGN-COV2 rapidly reduced viral load and associated symptoms in infected COVID-19 patients. The greatest treatment benefit was in patients who had not mounted their own effective immune response, suggesting that REGN-COV2 could provide a therapeutic substitute for the naturally occurring immune response.”
Regeneron has been improving and advancing the traditional drug development process through their proprietary VelociSuite technologies, such as VelocImmune which uses genetically humanized mice to produce optimized fully human antibodies. Using this technology, it generated two fully humanized antibodies REGN10933 and REGN10987 and combined them to specifically block the infectivity of SARS-CoV-2 through non-competitive binding to critical receptors’ binding domains.
REGN-COV2 is a cocktail of two antibodies, REGN10933 and REGN10987, targeting the spike protein of SARS-Cov-2. Spike proteins are present on the capsid of viral particles which can bind to host receptors leading to viral propagation in the host system. This decreases the chance of mutant viruses escaping treatment and protects against the increase of spike variants in the human population.
Since the drug targets two separate epitopes, it protects against the mutant drug-resistant virus. Pre-clinical studies have shown that REGN-COV2 can reduce the viral load in non-human primates. AstraZeneca is using a similar strategy where they are targeting multiple epitopes and using a combination of antibodies while other companies like Amgen and Eli Lilly are using the single antibody approach.
The preclinical and Phase 1 clinical study demonstrated that REGN-COV2 reduced the amount of virus as well as associated damage in the lungs of non-human primates. The first 275 patients in Phase 1 were randomized 1:1:1 to receive a one-time infusion of 8 grams of REGN-COV2 (high dose), or 2.4 grams (low dose) or placebo.
All patients underwent serology tests to check whether they have already developed antiviral antibodies on their own. Usually, without any treatment, patients tested with a seronegative of SARS-CoV-2, or absence of antiviral antibodies, required an average of 13 days to alleviate symptoms.
In contrast, patients who tested seropositive needed 7 days. Approximately 45% of patients were seropositive, 41% seronegative and 14% categorized as “other” due to unclear or unknown serology status. The results showed that patients with higher baseline viral levels tended to have a greater reduction in viral load at Day 7 with REGN-COV2 treatment and patients tested seronegative had greater benefits in terms of symptom alleviation.
Relative to the placebo treatment, patients with a viral load higher than 105 copies/ml had a 50-60% reduction, 106 copies/ml a 95% reduction, and 107 copies/ml a 99% reduction, each under REGN-COV2 treatment. Patients who tested seronegative only needed 8 days to alleviate symptoms in the high dose regimen and 6 days in the low dose. Besides that, patients who tested seronegative demonstrated a tremendous reduction in the additional number of medical visits. Both the doses were tolerated, and no deaths were reported. To date, 2000 patients have been enrolled and no safety concern has been reported. Following this exciting data, 1300 more patients will be recruited and followed for 29 days. Further, a Phase 3 trial, RECOVERY in hospitalized patients is underway.
David Weinreich, M.D., Senior Vice President and Head of Global Clinical Development at Regeneron said, “Thank you to the global investigators, sites, and patients who continue to work with us to conduct REGN-COV2 trials, especially given the unique challenges posed by the pandemic. We plan rapidly to submit detailed results from this analysis for publication in order to share insights with the public health and medical communities. Regeneron continues to enroll patients in this trial and all other ongoing late-stage trials evaluating REGN-COV2.”
The development of this drug has been partly funded by the Biomedical Advanced Research and Development Authority (BARDA). Roche has also invested in the drug. If successful, Roche will develop and manufacture the drug outside the US which will help increase global supply.
Editor: Rajaneesh K. Gopinath, Ph.D.
Related Article: COVID-19: J&J’s Vaccine Candidate Registers Strong Immune Response in Early Trials
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