Regeneron Pharmaceuticals, Inc. on January 26 announced positive initial results from an ongoing Phase 3 clinical trial evaluating REGEN-COV™ (casirivimab and imdevimab antibody cocktail) used as a passive vaccine for the prevention of COVID-19 in people at high risk of infection (due to household exposure to a COVID-19 patient).
The development and manufacturing of REGEN-COV has been funded in part with federal funds from the Biomedical Advanced Research and Development Authority (BARDA), part of the U.S. Department of Health and Human Services, Office of the Assistant Secretary for Preparedness and Response, under OT number: HHSO100201700020C. The trial is being run jointly with the National Institute of Allergy and Infectious Diseases (NIAID), part of the National Institutes of Health (NIH).
Regeneron is the second company in less than a week to report the potential for use of its monoclonal antibody therapy as a "passive vaccine" for individuals at high risk for COVID-19. Eli Lilly and Company announced on January 21 that its monoclonal antibody combination therapy, known as LY-CoV555 or bamlanivimab, was found to help prevent COVID-19 among nursing home residents and staff in a Phase 3 trial.
In the Regeneron passive vaccine trial, an exploratory analysis was conducted on the first approximately 400 evaluable individuals enrolled in the trial, who were randomized to receive passive vaccination with REGEN-COV (1,200 mg via subcutaneous injections) or placebo. Results included:
* Passive vaccination with REGEN-COV resulted in 100% prevention of symptomatic infection (8/223 placebo vs. 0/186 REGEN-COV), and approximately 50% lower overall rates of infection (symptomatic and asymptomatic) (23/223 placebo vs. 10/186 REGEN-COV).
* The lower number of infections occurring with REGEN-COV therapy were all asymptomatic, with decreased peak virus levels and short duration of viral shedding.
* Infections occurring in the placebo group had, on average, more than 100-fold higher peak viral load.
* Infections in the REGEN-COV group lasted no more than 1 week, while approximately 40% of infections in the placebo group lasted 3-4 weeks.
* No infected individuals in the REGEN-COV group had high viral loads (>10^4 copies/mL) compared to 62% of the infected placebo group (13/21 placebo vs. 0/9 REGEN-COV).
* REGEN-COV was associated with lower disease burden:
* Fewer total viral shedding weeks (44 weeks placebo vs. 9 weeks REGEN-COV).
* Fewer total high viral shedding weeks (>10^4 copies/mL) (22 weeks placebo vs. 0 weeks REGEN-COV).
* Fewer total symptomatic weeks (18 weeks placebo vs. 0 weeks REGEN-COV).
“These data using REGEN-COV as a passive vaccine suggest that it may both reduce transmission of the virus as well as reduce viral and disease burden in those who still get infected,” said George D. Yancopoulos, MD, PhD, President and Chief Scientific Officer at Regeneron. “Even with the emerging availability of active vaccines, we continue to see hundreds of thousands of people infected daily, actively spreading the virus to their close contacts. The REGEN-COV antibody cocktail may be able to help break this chain by providing immediate passive immunity to those at high risk of infection, in contrast to active vaccines which take weeks to provide protection. There are also many individuals who unfortunately may be immunocompromised and not respond well to an active vaccine or are otherwise unable to be vaccinated, and REGEN-COV has the potential to be an important option for these individuals. Overall, the REGEN-COV development program has demonstrated definitive anti-viral activity and the collective data strongly suggest it can be effective both as a therapeutic and as a passive vaccine.”
In the safety assessment, adverse events occurred more frequently in participants on placebo (18% placebo vs. 12% REGEN-COV); this difference was driven by the increased rate of SARS-CoV-2 infections in the placebo group. In the placebo group, there was one death and one COVID-19-related hospitalization; there were no deaths or COVID-19 hospitalizations in the treatment group. Injection site reactions occurred at a rate of approximately 2% in both treatment and placebo groups.
“In this prevention trial, REGEN-COV was given as injections rather than an infusion, which makes administration much more convenient and efficient for patients and overburdened healthcare providers and facilities,” said David Weinreich, MD, Executive Vice President and Head of Global Clinical Development at Regeneron. “It’s notable that the few infections that did occur after receiving REGEN-COV were all asymptomatic, and associated with markedly lower viral load and duration of viral shedding, potentially further reducing transmission. We look forward to seeing the full dataset early next quarter and will discuss the current results with regulatory authorities, including the potential to expand the Emergency Use Authorization.”
Under agreements with the U.S. government, Regeneron is supplying up to approximately 1.5 million doses of REGEN-COV for treatment of COVID-19 under the current Emergency Use Authorization (EUA). In November, REGEN-COV was granted an EUA by the U.S. Food and Drug Administration (FDA) for use in treating people with mild or moderate COVID-19 who are at high risk of developing severe symptoms and requiring hospitalization and are not currently hospitalized. The EUA is temporary and does not take the place of a formal biologics license application (BLA) review and approval process and the use of the antibody cocktail remains investigational. Evaluation of its safety and efficacy is ongoing in multiple clinical trials.