On August 4, Regeneron Pharmaceuticals and the U.S. National Institute of Allergy and Infectious Diseases (NIAID) launched a Phase III trial of REGN-COV2, Regeneron’s two-antibody cocktail to treat and prevent COVID-19. Research to date has demonstrated the cocktail’s effectiveness in rhesus macaques and hamsters. Today, Regeneron announced it was collaborating with Roche to develop and manufacture the cocktail globally. Regeneron will distribute REGN-COV2 in the U.S. and Roche will handle distribution outside the U.S.
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.
The cocktail has potential both as a preventative and treatment, although as a preventative it is not as long-lasting as a vaccine. The belief is that the antibodies can be injected into first-line responders, the elderly or immunocompromised, and individuals who have been exposed to the virus, and it will offer a month or two of resistance to infection.
“We are excited about the potential for one medicine to serve both as a treatment for those infected as well as protection for people exposed to the virus,” said Bill Anderson, chief executive officer of Roche Pharmaceuticals. “REGN-COV2 could be a critical line of defense against the COVID-19 pandemic. We’re committing our manufacturing expertise and capacity, and our global distribution network, to bring Regeneron’s potential antibody combination to as many people around the world as we possibly can.”
Under the terms of the deal, each company is dedicating a certain amount of manufacturing capacity to the cocktail each year. They have already started with the technology transfer required. Each company will handle their own distribution expenses in their designated territories. They will jointly fund and execute the ongoing Phase III prevention and Phase I healthy volunteer safety studies in addition to any more global studies for its potential for treating or preventing COVID-19. Roche will be mostly responsible for regulatory approvals outside the U.S. after the initial European approval, and running any more studies specifically needed by regulators outside the U.S.
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.”