Regeneron on Thursday began the first human trials of a medicine that's designed to treat, and possibly prevent, coronavirus infection.
The Tarrytown, New York-based biotech will test its treatment, a cocktail of two engineered antibodies, in two placebo-controlled studies of hospitalized and non-hospitalized COVID-19 patients. Should those studies show the treatment safe, Regeneron aims to start two additional trials later this month that would test the drug combination as a preventive therapy in healthy volunteers who are either at high risk of exposure, like healthcare workers and first responders, or have been exposed to the virus by someone close to them.
In one of the studies that began Thursday, of people who are in the hospital, Regeneron aims to improve outcomes — getting COVID-19 patients off ventilators or supportive oxygen, for instance. In the second study, of less sick "ambulatory" patients, Regeneron hopes to keep the disease from progressing, said Leah Lipsich, the company's vice president of Strategic Program Direction for Infectious Disease.
Regeneron aims to produce "meaningful data" from the first two studies within the next few months, and, if all were to go well, to have enough evidence to support emergency use toward the end of the year, Lipsich said in an interview with BioPharma Dive.
But a lot has to go right before that could happen. Like other drugmakers during the pandemic, Regeneron is moving at an exceedingly ambitious pace, attempting to do in months what normally takes years. That means learning about the coronavirus on the fly, and figuring out the best way to determine whether its medicine is having an impact.
To do so, Regeneron is using an "adaptive" trial that bridges across the usual three-phase design, Lipsich said. An independent monitoring board will regularly check the trial's progress to determine whether, in the following phase, the study goal needs to be modified, or whether more or less patients are needed to properly gauge an effect.
It's part of a strategy to get answers quickly, and reflects how drugmakers are developing treatments for a disease they don't yet fully understand. Researchers at the National Institute of Health, for example, switched a key study measure midway through a test of Gilead's antiviral remdesivir, which has since been cleared for emergency use by the Food and Drug Administration.
"The pace at which everyone is trying to move and analyze data and make decisions is unprecedented," Lipsich said. "We need to get data as fast as possible because people are dying."
Regeneron is one of a growing number of companies developing antibody drugs for COVID-19. These drugs are engineered versions of the immune proteins human bodies create to fight COVID-19 infections. Though they don't offer the long-lasting protection of a vaccine, they could nonetheless become extremely important tools to help ease the disease's burden on hospitals.
Antibodies' effects typically kick in quickly, rather than over the weeks or months sometimes needed for a vaccine to provide immunity. They might be able to treat sick patients, or to prevent infections from developing in those who have been exposed.
Regeneron also sees a greater role for antibodies among the elderly and those with weak immune systems, who are less likely to respond well to vaccines, Lipsich said.
On June 1, Eli Lilly became the first drugmaker to start a trial of a COVID-19 antibody drug, and its partner in China, Junshi Biosciences, has since followed with a second. Others are following fast with their own antibody programs, among them Amgen, AstraZeneca, AbbVie and Vir Biotechnology. AstraZeneca and Vir have both said they plan to start testing antibody candidates this summer.
These programs all have subtle differences, like the number of antibodies included in each treatment and whether they are modified in some way to boost their abilities.
Regeneron is the first company thus far to advance a cocktail of two engineered antibodies into clinical testing, although both Lilly and AstraZeneca are also planning to take a combination approach. Regeneron used a similar strategy to develop a three-drug antibody combination for Ebola that is currently under Food and Drug Administration review.
The thinking behind a cocktail is that multiple antibodies are able to grip the coronavirus more tightly, keeping it from escaping and heading off inadvertent selection of genetic mutants that can evade treatment. Two papers that will be published by the journal Science on Monday show that, in preclinical tests, Regeneron's cocktail was able to prevent viral escape, something a number of single antibodies the company tested couldn't do.
"It's almost a mathematical impossibility for the virus to escape from both of those antibodies at the same time," Lipsich said.
But that strategy comes with a cost. It's complex and expensive to manufacture even one antibody at scale during a pandemic, let alone two. Regeneron's chief scientific officer George Yancopoulos said at a virtual meeting hosted this week by the trade group BIO that the company, despite its size and experience developing antibody drugs, would likely need manufacturing alliances to produce sufficient supply. Regeneron is developing an intravenous formulation of its antibody for use in treating existing infections, and a lower-dose subcutaneous version for use in preventing infections.
The company is planning on making hundreds of thousands of doses per month from its existing manufacturing plants in the U.S. and Ireland, but is looking for more help, Lipsich said. "We're talking to everyone out there," she said.