It’s all hands on deck as government agencies, researchers, startups, biopharma giants, health care workers and payers combine their resources to develop proven COVID-19 therapies that can be ready for market by fall when the pandemic is expected to pick up steam again in the U.S. and other northern reaches of the world.

Since vaccines still will be several months away, therapies will be the only hope for an exhausted health care system. “It’s a pretty small toolbox,” former FDA Commissioner Scott Gottlieb said Monday in a Duke-Margolis Center webinar on developing a therapeutic response to COVID-19.

Although more than 200 therapeutics are in development, only a few are expected to be approvable by fall when schools and colleges reopen and business travel resumes, creating opportunities for the coronavirus to spread. The therapies closest to launch are mostly antivirals that are being repurposed and monoclonal antibodies.

Their development timeline will be impacted by clinical trials and manufacturing capacity. With the pandemic expected to subside during the hot, humid months in the U.S., getting a potential therapy through clinical trials in July and August, especially for prophylactic use, could prove challenging, Gottlieb said. Another challenge is designing a clinical trial that doesn’t add to the load of frontline doctors and nurses.

Then there’s the question of scaling up manufacturing of a new drug that quickly. Gottlieb said several drug companies are moving the manufacture of some of their existing products to the EU to free up U.S. manufacturing capacity for new COVID-19 therapies.

Prioritizing development

On the good news side, NIH Director Francis Collins said data are expected soon from a randomized controlled trial of Foster City, Calif.-based Gilead Sciences Inc.’s remdesivir. The trial stopped enrolling last week with 900 participants – 400 more than the initial target. If the data show the antiviral is effective against the coronavirus, other therapies still will be needed, Collins said, citing experience with HIV.

To prioritize the development of potential therapies that could be available by fall, the NIH Friday launched the Accelerating COVID-19 Therapeutic Interventions and Vaccines (ACTIV) partnership, bringing together 16 biopharma companies and several government agencies. The partners will look at as many as 600 drug candidates that have already been tested in people and that could immediately be tested in phase II COVID-19 trials, Collins said.

ACTIV members will sift through those candidates to identify those that have the best chance of working against the coronavirus and for which there is manufacturing capacity. In the first wave, the goal is to narrow it down to six to eight potential therapies with different mechanisms of action. The candidates would be tested in a master protocol trial, possibly with a common control arm, with the hope of demonstrating, by July or August, that at least two or three of them work, Collins said.

“All this is moving at rocket pace,” he said, adding that what’s different about ACTIV is the level of collaboration between government and industry.

This is what the government can and should be doing, even though it requires the government to pick some winners at the outset, Gottlieb said. “We’re dealing with scarce resources,” so the government can’t focus on every potential therapy, he said. Instead, it needs to look at those therapies that can deliver the biggest benefit in the shortest amount of time.

Meanwhile, a number of biopharma companies are working on their own to develop potential COVID-19 therapies in time for a fall resurgence of the pandemic. During the webinar, George Yancopoulos, president and chief scientific officer of Tarrytown, N.Y.-based Regeneron Inc., gave an update on his company’s COVID-19 development. Human monoclonal antibodies developed using Regeneron’s Velocisuite technologies are a month or two away from beginning trials, he said.

The company has tested several antibody cocktails against the known variants of the virus and is planning trials for use as a prophylactic, in early stage infections and in hospitalized patients. Regeneron also is preparing its interleukin-6 (IL-6) agent for a clinical trial assessing it in critical care patients. The trial will test a hypothesis based on the agent’s use in uncontrolled trials in China.

Vir Biotechnology Inc., of San Francisco, plans to move a promising antibody into clinical trials this summer, Vir CEO George Scangos said during the webinar. While the company intends to do the trials in the U.S., it’s lining up sites in other countries in case the course of the coronavirus makes U.S. summer enrollment problematic. Vir also is developing antibody combinations to move into trials.

While manufacturing concerns usually follow development of a drug, Vir is lining up commercial manufacturing capacity before the antibody even proves itself in a trial. Scangos acknowledged that’s a risk, but he said the only thing that might be worse than not having a therapy is having a therapy with no capacity to manufacture it. Besides, if the antibody doesn’t work, someone else could use the manufacturing capacity, Scangos added.

In responding to the pandemic, drug companies can’t afford to make development a linear process, agreed Chad Robins, CEO of Seattle-based Adaptive Biotechnologies Inc., which is partnering on a cell-based COVID-19 diagnostic with Microsoft and is working with Amgen Inc., of Thousand Oaks, Calif., on developing antibodies to fight the coronavirus. Drug companies have to address development and manufacturing issues all at once, Robins said.

Whether they come from company or team efforts, “I hope everybody’s antibodies will work,” Scangos said, adding that they may all be needed around the world before a COVID-19 vaccine becomes available.

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