A ‘bridge to a vaccine’: The race to roll out antibody-based Covid-19 drugs

A German researcher checks plasma collected from a recovered Covid-19 patient. Plasma is still a bottleneck for some pharmaceutical companies working on antibody-based drugs.
A German researcher checks plasma collected from a recovered Covid-19 patient. Plasma is still a bottleneck for some pharmaceutical companies working on antibody-based drugs.
Image: Andreas Gebert/Reuters
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The world is not likely to see a vaccine for SARS-CoV-2 until next year, and there’s still no drug engineered to fight the virus. Studies of the malaria drug hydroxychloroquine, which has been touted by President Trump, have not conclusively shown an effect against Covid-19. Plasma transfusions, which deliver antibodies from blood donated by recovered Covid-19 patients, are undergoing trials in a few hospitals, but remain in short supply.

In the meantime, a growing number of pharmaceutical companies are scrambling to roll out what will likely be the first generation of drugs specific to Covid-19.

Like plasma transfusions, these drugs are built on antibodies. But they’re delivered in a concentration that aims to be more effective, consistent, and able to be mass-produced. Such drugs are commonplace in treating cancer, rheumatoid arthritis, infectious diseases like Ebola, and other conditions, and represent a $50 billion annual market in the US that includes six of the country’s top 15 selling drugs. 

Several companies are preparing to start clinical trials with an antibody-based Covid-19 drug, and several project they could be available by the fall.  

“There’s definitely a race to do this,” said Tom Moran, director of the Center for Therapeutic Antibody Development at Mount Sinai School of Medicine. “A lot of people believe that this could be a bridge to a vaccine. And monoclonal antibodies are the number-one grossing drugs on the market today, so it’s not far-fetched.”

On Monday, pharma giant GlaxoSmithKline announced a $250 million investment in San Francisco-based Vir Biotechnologies to support its development of an antibody drug for the novel coronavirus. The same day, Japanese drug producer Takeda, which had been working on an antibody drug since early March, said it would partner with Pennsylvania-based CSL Behring and a number of smaller biopharmaceutical companies to scale up its effort and pool resources, especially stores of plasma. Last week, the federal government gave a $14.5 million grant to Maryland-based Emergent BioSolutions to work on an antibody drug. Other competitors in the race include AstraZeneca and Regeneron

When faced with a virus, the human immune system deploys antibodies to latch on to the invader, preventing it from replicating itself or entering our cells. Antibodies are generally Y-shaped, but our bodies come stocked with billions of slight variations that work together to respond to countless invaders. In a typical plasma transfusion, all the antibodies that responded to an infection are delivered to the sick patient en masse, and usually one donation is only enough for one treatment. 

But for any given virus, some antibodies will be more effective than others, and the concentration of antibodies can differ greatly from person to person. Plus, there’s a clear public health need to produce hundreds of thousands of doses. That’s where antibody drugs come in. 

The basic goal is to identify the one or more antibodies that are most effective in neutralizing SARS-CoV-2, refine and mass-produce them in labs, and pack a consistent concentration of them into shots. Healthcare workers and other high-risk individuals could get the shots as a preventative measure, and they could be given to sick patients to prevent their symptoms from escalating. The shots could be monoclonal, with just a single form of antibody, or a “polyclonal” cocktail with multiple antibodies. 

Some companies, like Takeda and Vir, are working with antibodies taken from human blood. Vir, for example, started out by looking at antibodies in blood from patients who recovered from the earlier SARS epidemic, and identified two that seemed to also neutralize the new coronavirus. The company is now reproducing those with immune cell cultures in its labs, while looking for additional antibodies in blood donated by recovered Covid-19 patients. Lindy Devereux, a spokesperson, said that the company received hundreds of responses in response to a public call for donations. With the antibodies identified and isolated, the company will be able to ramp up production even without a supply of plasma. 

“Access to convalescent plasma was a bottleneck for many research organizations early on, including us, but it is not an issue any more,” she said. 

For the Takeda coalition, whose approach involves concentrating a wide array of antibodies from recovered patients, access to plasma is still a bottleneck. Hundreds of liters are required before a factory can start manufacturing the drug, and the supply is still very limited. So companies that would otherwise be competitors were forced to team up—a collaboration which will ultimately include sharing profits, but won’t require the companies to share any proprietary technology—to get the raw materials, said Julie Kim, who leads plasma-derived therapies for Takeda. 

“The special circumstances of this outbreak have created an environment where many of us have said it doesn’t make sense to compete,” she said. “Rather than each individual company sitting there waiting for the plasma to get to a certain level, we can pool it and send it to one centralized manufacturing site in the US.”

Another workaround to the plasma supply problem is to harvest the antibodies from animals. Regeneron has a proprietary breed of genetically engineered mice that produce human antibodies when infected with pathogens—in this case, lab-grown cells that mimic the distinctive spiky shape of SARS-CoV-2. Emergent is using a similar approach with horses, whose natural immune systems are similar to humans.

Christos Kyratsous, lead infectious disease scientist at Regeneron, said that using a cocktail of antibodies, rather than just one, helps ensure that the drug will stay effective even as the virus continues to mutate, and could even allow the same drugs to be used on any future coronavirus.

“We use the second antibody here like an insurance policy,” he said. “And we’re trying to select antibodies that bind to sites on the virus that are as conserved as possible [over time].”

Because monoclonal antibody drugs are commonplace and all basically work the same way, they tend to speed through FDA approval even in normal circumstances, Moran said, and should be able to skip some steps of that process given the current crisis. And the antibodies can stick around in the immune system for weeks, said Mandy Oglesby-Sherrouse, a professor of Pharmaceutical Sciences at the University of Maryland (healthcare workers or others using antibody drugs as a prophylaxis would need to re-up every month or so).

“Even with monoclonal treatments that are developed in a research lab, it’s a natural approach,” she said. Making use of antibodies “is something our bodies know how to do.”

But the approach isn’t without risk, Oglesby-Sherrouse said. In a peer-reviewed study last year of lab monkeys infected with the older SARS coronavirus, antibody drugs were found to severely worsen respiratory symptoms after they provoked a massive inflammatory response in the lungs. That will be something to watch for in trials this summer.

“If you stimulate the wrong kind of response,” Oglesby-Sherrouse said, “it could actually make people much worse.”