Before Regeneron Pharmaceuticals’ experimental treatment for combatting COVID-19 was given to President Donald Trump earlier this month, the antibody cocktail was tested on animals at the Texas Biomedical Research Institute in San Antonio.
In order to move the drug – Regeneron’s REGN-COV2 monoclonal antibody cocktail – to clinical trials, the treatment first had to undergo preclinical testing, said Lisa Cruz, vice president of corporate communications at Texas Biomed. The research institute performed trials on three different primates; marmosets, baboons, and rhesus macaques.
“We think it is important that people understand how these drugs move through the entire development process from basic discovery, through preclinical testing and eventual distribution,” Cruz said.
Regeneron’s antibody cocktail hasn’t been approved by the federal Food and Drug Administration but attracted attention as Trump credited the treatment as a “cure” after he tested positive for the coronavirus and was briefly hospitalized. The therapy is not available to the general public, and Regeneron officials have stressed that large clinical trials will need to be completed before the treatment’s effectiveness is known.
Testing with the drug and other COVID-19 treatments began at Texas Biomed in March just weeks after the coronavirus pandemic began to sweep through the United States, said Texas Biomed President and CEO Larry Schlesinger.
“The study we did at Texas Biomed was actually looking at a cocktail – so two drugs, two antibodies – to determine if we can demonstrate efficacy in nonhuman primate models,” said Ricardo Carrion Jr., the program co-lead in disease intervention and prevention for the institute’s Southwest National Primate Research Center.
Regeneron’s REGN-COV2 antibody cocktail uses two types of antibodies that are specific to humans so they will not trigger an allergic reaction, Schlesinger said. Regeneron engineered the antibodies so they bind tightly and effectively to the coronavirus spike protein, Carrion explained. By doing so, they inactivate or neutralize the virus cell so it is no longer able to bind to host cells and infect them, he said.
Texas Biomed researchers began studying the effects of the coronavirus and different treatments for it, such as Regeneron’s REGN-COV2 antibody cocktail, in early April, Schlesinger said. The marmosets, baboons, and rhesus macaques used to test treatments were among the primate species housed at the primate center on Texas Biomed’s campus.
One test used the antibody cocktail as a prophylactic treatment, meaning it was given to the primates before they were exposed to the coronavirus to see if it worked as a preventative, Carrion said. A second test tried the antibody cocktail as a therapy, so it was given to the primates after they were exposed to the coronavirus, he said.
The idea of having two antibodies in the cocktail is that the coronavirus is evolving quickly and mutating, so having two types of antibodies helps keep it under control better, Carrion said.
“What was found out was that when you do this prophylactically and also therapeutically, you have a reduction in the amount of virus present in the animal,” Carrion said. “[The animal] also has a reduction in some of the lesions we see in the lungs and other tissue in both cases – more so with the prophylactics as we gave it earlier, versus a therapeutic.”
Texas Biomed’s relationship with Regeneron dates back to the institute’s Ebola research that began in 2015, he said. In January, as the novel coronavirus had emerged in China and was beginning to spread elsewhere, Carrion attended a meeting for emerging viral diseases where the virus was discussed.
“I met with some of the Regeneron folks and they were saying ‘We just finished, possibly having this cure for Ebola virus, we’re starting up some COVID work – would you guys be available to test it?’ So, from that point of time when they had their antibody developed, they were able to contact us.”
Following the testing at Texas Biomed, Regeneron’s REGN-COV2 antibody cocktail advanced into human trials and is now in a Phase Three clinical trial, which is the largest phase, Schlesinger said, noting there is no emergency use authorization yet for the treatment. Trump received the antibody cocktail under a “compassionate use” authorization, a special exception in which an unapproved drug is given to someone outside of clinical trials at the request of a doctor.
Regeneron is currently pursuing an emergency use authorization through the Food and Drug Administration for the cocktail, but cannot mass-produce the product without approval or license to do so. Still, even after mass production begins, scientists worry there won’t be enough doses to fill demand.
Carrion said when he first heard the president would be receiving one of the very treatments he and his coworkers had tested, he was hopeful it would work.
“I thought, ‘I hope it works, because it proves a model,’” he said with a laugh. “My thought was like, ‘I really hope this works and it helps [us] validate the model more.’”