Regeneron Pharmaceuticals, with the U.S. National Institute of Allergy and Infectious Diseases (NIAID), is launching Phase III trials of REGN-COV2, the company’s two-antibody cocktail for the treatment and prevention of COVID-19.
There are specifically two trials. A Phase III trial will study if REGN-COV2 can prevent infection in uninfected people who have had close exposure to a COVID-19 patient. The drug has also been advanced into the Phase II/III portion of two adaptive Phase I/II/III trials evaluating the cocktail in treating hospitalized and non-hospitalized patients with COVID-19.
A Phase I trial in 30 hospitalized and non-hospitalized patients with COVID-19 received a positive review from the Independent Data Monitoring Committee.
The Phase III prevention study will be run at about 100 locations and enroll about 2,000 people in the U.S. The Phase II/III treatment trials in hospitalized patients will evaluate about 1,850 hospitalized patients and 1,050 non-hospitalized patients, and is planned for about 150 sites in the U.S., Brazil, Mexico, and Chile. It will study virologic and clinical endpoints. Preliminary data is expected later this summer.
“We are running simultaneous adaptive trials in order to move as quickly as possible to provide a potential solution to prevent and treat COVID-19 infections, even in the midst of an ongoing global pandemic,” said George D. Yancopoulos, co-founder, president and chief scientific officer of Regeneron. “We are pleased to collaborate with NIAID to study REGN-COV2 in our quest to further prevent the spread of the virus with an anti-viral antibody cocktail that could be available much sooner than a vaccine.”
Using its proprietary VelocImmune mice, Regeneron screened thousands of fully-human antibodies. The mice have been genetically modified to have a human immune system. They also evaluated antibodies isolated from people who have recovered from COVID-19. They then chose the two most potent, non-competing antibodies that were most effective at neutralizing SARS-CoV-2, the virus that causes COVID-19. They then scaled up the dual-antibody cocktail for clinical use with the company’s own VelociMab and manufacturing capabilities.
The two antibodies bind non-competitively to the receptor binding domain of the virus’s spike (S) protein. This decreases the ability of mutant viruses to avoid treatment and protects against spike variants that have evolved in the human population.
On June 11, the company announced the publication of two scientific articles describing the effectiveness of REGN-COV2 in the journal Science. The first paper was, “Studies in humanized mice and convalescent humans yield a SARS-COV-2 antibody cocktail.”
The second paper was “Antibody Cocktail to SARS-CoV-2 Spike Protein Prevents Rapid Mutational Escape Seen with Individual Antibodies.”
“Our manuscripts describe the results of a cross-functional, comprehensive study, aiming to generate, isolate, select and functionally characterize human antibodies against SARS-CoV-2,” said Christos Kyratsous, vice president of Research, Infectious Diseases and Viral Vector Technologies at Regeneron. “We previously used the same technologies and cocktail approach to develop REGN-EB3, a novel triple antibody treatment for Ebola that demonstrated safety and efficacy versus the standard of care in a clinical trial in the Democratic Republic of Congo. We hope to see similar success with this program and help improve outcomes against this terrible disease.”
Regeneron, along with Sanofi, was also testing their Kevzara (sarilumab) in COVID-19 patients on ventilators, but the drug failed to hit the primary and key secondary endpoints. They announced the results on July 2. As a result, the U.S.-based clinical trial was halted, including a second arm of patients who received 800 mg doses of the drug. Kevzara is approved to treat adults with moderately to severely active rheumatoid arthritis. It binds to the IL-6 receptors and inhibits IL-6-mediated signaling. IL-6 is an immune protein found in high levels in rheumatoid arthritis patients and is linked to disease activity, joint destruction, and other systemic issues. The drug was being evaluated for its ability to decrease the overactive inflammatory response seen in COVID-19.