Regeneron Pharmaceuticals said today it has launched the first clinical trial of its dual-antibody “cocktail” designed to both prevent and treat COVID-19, as well as prevent viral escape.

The cocktail, now named REGN-COV2, consists of two antibodies—REGN10933 and REGN10987—that are designed to bind non-competitively to the receptor binding domain of SARS-CoV-2’s spike protein. Regeneron says that such binding diminishes the ability of mutant viruses to escape treatment—with details from preclinical research to be published in upcoming research studies.

Those studies, Regeneron added, will show that in the setting of a single therapeutic antibody that blocks the ability of a virus to infect healthy cells, spontaneously arising mutant forms of the virus can evade the antibody’s blocking action, or “escape.” These mutants survive and proliferate despite the single antibody treatment, then may ultimately become the dominant strain of the virus.

To prevent that possibility, Regeneron is pursuing a multi-antibody cocktail approach designed to decrease the potential for the virus to escape.

“The antibody cocktail approach may also have long-term utility for elderly and immuno-compromised patients, who often do not respond well to vaccines,” George D. Yancopoulos, MD, PhD, co-founder, president and chief scientific officer of Regeneron, said in a statement. “REGN-COV2 could have a major impact on public health by slowing spread of the virus and providing a needed treatment for those already sick—and could be available much sooner than a vaccine.

Regeneron offered no timeframe in today’s statement. However, addressing analysts on Regeneron’s quarterly conference call in April, founder, president, and CEO Leonard S. Schleifer, MD, PhD, said “it is possible” that the antibody cocktail may be available to patients by the end of summer or this fall.

Front runner candidate

Regeneron’s antibody cocktail is among 18 “front runner” candidates among the 230+ COVID-19 therapeutics detailed in GEN’s updated “COVID-19 Drug & Vaccine Candidate Tracker.”

The two antibodies, according to Regeneron, were the two most potent, non-competing and virus-neutralizing antibodies selected from thousands of fully-human antibodies produced by the company’s proprietary VelocImmune® mice, which are genetically-modified to have a human immune system, as well as antibodies isolated from humans who have recovered from COVID-19. The antibodies were selected and scaled up for clinical use through the company’s in-house VelociMab® and manufacturing capabilities.

The cocktail approach is similar to that employed by Regeneron against Ebola in its development of REGN-EB3. That triple antibody treatment is under FDA priority review, with a target action date of October 25, 2020, based on successful results from the Phase III PALM clinical trial conducted in the Congo.

Regeneron isn’t the only biopharma giant pursuing an antibody cocktail. Eli Lilly on Monday announced the start of clinical studies for a second anti-COVID-19 antibody, JS016, which Lilly is co-developing with Junshi Biosciences. Lilly said Junshi had dosed the first healthy volunteer in a Chinese Phase I trial of JS016, for which Junshi leads development in Greater China, while Lilly holds rights in the rest of the world—including the U.S., where it plans to begin dosing the first patient in a complementary clinical trial.

Last week, Lilly and Abcellera said they began dosing the first patients in a Phase I trial for Lilly’s other announced antibody candidate against COVID-19, LY-CoV555.

Four study populations

Regeneron said its clinical program for REGN-COV2 will consist of four separate study populations: Hospitalized COVID-19 patients; non-hospitalized symptomatic COVID-19 patients; uninfected people in groups that are at high-risk of exposure, such as healthcare workers or first responders; and uninfected people with close exposure to a COVID-19 patient, such as the patient’s housemate.

The first two adaptive Phase I/II/III studies will assess REGN-COV2 in hospitalized and non-hospitalized patients with COVID-19. The Phase I portion will focus on virologic and safety endpoints, while the Phase II portion will center on virologic and clinical endpoints. Data from the Phase I and Phase II studies will be used to refine the endpoints and determine size for eventual Phase III studies.

“If and when a vaccine arrives, there is still a very high likelihood that there will be a need for antibody approaches for those who don’t respond well to the vaccine, or who have disease and haven’t been vaccinated,” Yancopoulos said Monday during “Leveraging Innovative Technology to Treat COVID-19 Patients,” a panel discussion held as part of the Biotechnology Innovation Organization’s (BIO) BIO Digital, the virtual 2020 International Convention being held through Friday.

Yancopoulos said in April that Regeneron was committing its Industrial Operations and Product Supply manufacturing facility in Rensselaer, NY, near Albany toward manufacturing the antibody cocktail, “which on its own could supply hundreds of thousands, if not over the course of time, maybe even on the order of a million or so doses per month.”

REGN-COV2’s preclinical development and preclinical/clinical manufacturing has been funded in part with federal funds from the Biomedical Advanced Research and Development Authority (BARDA) under OT number: HHSO100201700020C.

BARDA earlier this year committed nearly $16.4 million ($16,368,388) toward development of another Regeneron COVID-19 candidate. The company is partnering with Sanofi to reposition Kevzara® (sarilumab), the Interleukin-6 (IL-6) receptor antagonist the companies have co-developed as an arthritis drug, as a treatment targeting the virus.

Speaking Monday at BIO Digital, Yancopoulos offered a heads-up that the start of clinical studies was “days away.”

“We think this approach really has an opportunity and a hope that it could really make a substantial benefit in various aspects of this disease,” Yancopoulos said. “It can, like a vaccine, prevent infection in people if it’s given prophylactically. But we think the evidence suggests it will be also able to treat very effectively people in the early stages of infection as well as perhaps also reversing serious disease in people in the later stages of infection.”

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