Last week, the U.S. Food and Drug Administration granted initial approval to an experimental monoclonal COVID-19 drug, paving the way for more widespread use of the promising antibody-based therapy in coming months. Taken in tandem with Pfizer announcing its leading coronavirus vaccine candidate had been 90 percent effective in advanced trials, it was welcome news in a country experiencing well over 100,000 new COVID-19 cases a day.
But bottlenecks are likely to slow doctors’ efforts to include monoclonal antibodies in the standard of care for COVID-19. The coming weeks and months will amount to a race to develop clever ways to scale up production and distribution of these therapies even as hospitals are overwhelmed—and deaths spiral.
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“I’m bullish on monoclonals, but they’re not going to fly off shelves and into patients,” John Mellors, the chief of the Division of Infectious Diseases at the University of Pittsburgh who’s overseeing development of a monoclonal COVID therapy called Ab8, told The Daily Beast.
Monoclonals are lab-grown proteins that work by attaching to the spike proteins on the surface of the coronavirus. This can prevent the pathogen from adhering to the patients’ own cells and causing an infection. It might also help to reduce the severity of symptoms in people who’ve already been infected.
The FDA gave its tentative thumbs-up to a monoclonal from Indiana pharma Eli Lilly last Monday. The emergency-use authorization, or EUA, allows clinicians to treat patients at risk of developing severe COVID cases while the drug is still in large-scale, phase 3 trials. In many cases, full authorization for general use eventually follows an EUA.
But Eli Lilly’s monoclonal “bamlanivimab” works best in out-patient treatment on people with recently diagnosed mild-to-moderate COVID-19, the company said in a note to investors. “Patients treated with bamlanivimab showed reduced viral load and rates of symptoms and hospitalization,” Eli Lilly stated. The company was previously ordered to halt a therapy trial on hospitalized patients over safety concerns, while plowing head with trials on those experiencing less severe cases.
New York pharma Regeneron is also developing a monoclonal COVID therapy. President Donald Trump got a dose of that Regeneron drug under a so-called “compassionate use” exception after testing positive for the coronavirus in early October. Regeneron has applied for an EUA for its monoclonal, which is in the final stages of phase-three trials.
Anticipating successful conclusions to their respective trials and eventual sign-offs from the FDA, both Eli Lilly and Regeneron have been ramping up production of their monoclonals. (Pitt’s monoclonal is still in early trials.)
Lilly expects to produce a million doses by the end of 2020, company spokesperson Dani Barnhizer told The Daily Beast. Back in October, the federal government bought 300,000 of those doses for $375 million. Production rates should increase in early 2021 as more factories come online, Barnhizer added.
Regeneron spokesperson Alexandra Bowie told The Daily Beast the company could have around 80,000 doses on hand by the time the FDA gives the drug emergency approval, potentially in the coming weeks. Production could increase to 300,000 doses by mid-January, Bowie said. The feds juiced Regeneron’s production ramp-up this summer with a $450-million order for the monoclonal drug.
But even these hundreds of thousands of doses are a drop in the bucket at a time when COVID cases are increasing fast. Health authorities reported more than 184,000 new cases across the United States on Friday—a new record. The SARS-CoV-2 virus has infected more than 50 million people worldwide since December and killed more than 1.2 million, including nearly 250,000 in the United States.
“We’re surging right now,” Mellors said. “There’s no way we can treat the surge with monoclonals.”
Ramping up monoclonal production is hard. Technically, monoclonals aren’t drugs. They’re “biologics,” meaning they include live cells. Producing biologics is “not as easy as synthesizing a chemical and putting it in a pill,” Lawrence Corey, a professor of medicine and laboratory medicine at the University of Washington, told The Daily Beast.
“Because antibody manufacturing involves growing live cells, it is rather time- and cost-intensive, and requires specialized expertise and equipment,” Bowie explained.
Some shortcuts are possible. Many factories grow biologics in big steel vats that require careful cleaning. But more and more facilities are switching to disposable plastic vessels that aren’t as maintenance-intensive, Corey explained. “The technology has gotten better and better,” he said.
There are other obstacles. Monoclonal doses are big. Where some therapies come in doses of a few hundred milligrams, many monoclonal doses are measured in grams. Trump’s Regeneron dose was a whopping eight grams.
The size of the dose matters—a lot. A dose of several grams is too big for subcutaneous injection. Instead, you have to get it through an intravenous drip.
In many hospitals and clinics, I.V.s are administered in one central location. But it’s not safe to mix COVID and non-COVID patients, especially considering that many non-COVID patients getting I.V. drips have compromised immune systems that make them especially vulnerable to the coronavirus.
Mellors and his team at Pitt set up special facilities for administering their monoclonal to test subjects, graduating from a tent to larger and larger trailers. “Finding appropriate space has been a challenge,” Mellors said.
William Hartman, a University of Wisconsin researcher who is involved in Regeneron’s monoclonal trials, said his team took over the second story of an urgent care facility with a separate entrance for the COVID patients. “We are fortunate to have this space and the equipment necessary to carry this out, but it would be an expensive undertaking for many places to devote the resources necessary to care for COVID outpatients,” he said.
Smaller doses could provide for different methods of administering the monoclonal therapies, potentially allowing clinicians to use existing facilities. Eli Lilly is organizing a trial of a new version of its biologic that comes in smaller doses, Barnhizer said.
Logistical complications notwithstanding, monoclonals are still some of the most promising new therapies to come out of crash R&D efforts. We won’t know for sure exactly how effective monoclonals are until all the trials are complete. But early indications are encouraging. and it’s worth the effort to set up facilities for administering the therapies, experts told The Daily Beast.
“I think these will be game-changers that can keep patients out of hospitals and on a quicker road to recovery,” Hartman said.
Still, getting the maximum benefit from monoclonals is going to take investment and some big logistical tweaks. And time—something the U.S. hospital system is running out of, fast.
