Researchers have begun testing what appears to be the first new medicine developed specifically against Covid-19, in a milestone for drug companies aiming to combat the disease, the medicine’s makers said Monday.
The medicine, a human-made antibody against the coronavirus that causes the disease, was discovered by a Vancouver company, AbCellera, and is being developed by Eli Lilly, the Indianapolis-based drug giant. Two other efforts, one from the biotechnology firm Regeneron and another from the partnership of Vir Biotechnology and GlaxoSmithKline, are expected to begin testing of their own antibody drugs soon. Lilly’s current study will only test the drug for obvious side effects, giving it to 32 people at various doses.
“We’re not racing against each other,” Daniel Skovronsky, the chief scientific officer at Eli Lilly, said of the other companies. “We’re racing against the death toll from the virus. I hope there will be multiple successful [antibody drugs]. I expect there will be.”
The timeline for each drug could vary depending on exactly what steps each company takes, but the medicines are important because if one works it might provide a way to treat infection with the coronavirus, SARS-CoV-2, or to prevent infection before the end of the year. Skovronsky said that depending on the characteristics of each antibody drug, it might be possible for companies to produce hundreds of thousands or millions of doses by the end of the year.
Vaccines work by teaching the body to make its own antibodies, which prevent infection. Researchers are also experimenting with giving patients blood from those who have recovered, called convalescent plasma, so that sick people can benefit from the antibodies in that blood. But this will never be a large-scale treatment. The advantage of an antibody drug is that researchers could select a particularly effective antibody out of the thousands of different SARS-CoV-2 antibodies that might exist in even one patient, and then manufacture it at scale.
“Ultimately, what we would hope is that this would be an effective treatment that would provide very strongly neutralizing antibodies to lower the virus and help patients recover,” said Mark Mulligan, the director of the vaccine center at New York University Langone Health, who is one of the doctors working in the study that Lilly is funding.
Another hope is that it might prevent infection. Mulligan said NYU had just infused its first patient with the antibody, giving it over 30 minutes intravenously. The antibody will stay in his body for weeks.
Skovronsky said he imagines giving antibody drugs to elderly patients, for whom vaccines might not be as effective, preventing infections in nursing homes, where much of the death toll has been, or for people who know they have been recently exposed to someone with Covid-19. Those studies will be difficult to run, he said, and will not begin until after the current study has finished.
There is no way to know for sure if any antibody drug will be effective, or how they will compare to one another. “I think the only way to know that for sure is to do the human, you know, human investigations and let the data fall out as they do,” Mulligan said. One in five drugs for infectious disease that begins studies eventually reaches patients, according to data collected by the Biotechnology Industry Organization.
And the current efforts are all trying to compress a drug development process that takes years into months. AbCellera and Eli Lilly only started work on this antibody drug in late February.
Carl Hansen, AbCellera’s founder and CEO, said his company had been working for years with the Defense Advanced Research Projects Agency, part of the U.S. Department of Defense, to figure out how to develop medicines quickly in a pandemic. Last year, the company, working with the Vaccine Research Center of the National Institute of Allergy and Infectious Diseases, had run a simulation of its capabilities to take on a pandemic flu. It had already been planning to attempt to demonstrate its capabilities against a coronavirus this year. Then, the Covid-19 pandemic emerged.
Hansen remembers that, on the day when the first U.S. case of Covid-19 was reported, he called a meeting of his 150-person staff. “We’ve been training for this and this is the real thing,” he decided. “We should drop the simulation.”
In late February, Hansen said AbCellera obtained a blood sample from a patient with Covid-19 and started screening using a unique technology. Antibodies are made by white blood cells called B cells. AbCellera uses a credit-card-sized device to isolate individual B cells in tiny tubes, and to collect the antibodies they make, and then to obtain those specific B cells and the sequences of the antibodies. That allowed AbCellera to find more than 550 antibodies that appeared as if they might work against the virus.
Finding such antibodies is just the first step. In March, Regeneron said that it, too, had found hundreds of such antibodies. Vir made similar claims, as have several other groups. Last week, Nature published data from another Eli Lilly collaborator, Junshi Biosciences of Shanghai, showing that its SARS-CoV-2 antibody reduced virus levels in rhesus macaques, a hurdle the AbCellera antibody has not cleared.
Hansen said he knew that his company needed a large partner to help test and manufacture its antibody. AbCellera had been negotiating a deal with Lilly, and Lilly was planning to invest in the company. He reached out to the company on March 5. But he then flew to San Francisco, planning to have other meetings about the project.
Skovronsky, who is based in Indianapolis, was sitting in a meeting at Lilly’s San Diego research labs when an employee told him about AbCellera’s efforts. “I said yes, absolutely, we need to prioritize that,” Skovronsky remembered. “Literally, from reading the email to making the decision, it couldn’t have been 10 seconds.”
Hansen booked a flight from San Francisco to Indianapolis, where he and Skovronsky met and discussed the process. They shook hands on a deal. Hansen rushed off to catch a plane to visit his partners at NIAID, only to find that they didn’t need to see him. It was his last business trip.
Over the course of his trip, the gravity of the situation sank in. It had been clear that Covid-19 was a big problem for the world, but it hadn’t seemed like much of a threat in Vancouver. But in San Francisco, some people wouldn’t shake his hand.
Recently, Hansen was on a video call with his team — an important one — when he got a text from Skovronsky telling him that the antibody would be moving into a clinical trial in humans. He could see his face get flushed, and felt a tear in his eye. He had shivers. He can’t remember the last 20 minutes of the call. You might go a lifetime, he said, doing good work in biotechnology without building a technology that can really add something important to the world. The speed of this effort, and the desperation, have further amplified his emotions.
Now comes the hard part: figuring out if these antibodies — or others, including two more Lilly itself is developing — will prove effective as treatments, or as ways of preventing infection.
“It feels it feels like we’re making history,” said Skovronsky. Just three months after Covid-19 became a global pandemic, the pharmaceutical industry has been able to confront it, he said. “This has got to be a new phase in the fight.”