This New COVID-19 Therapy Could Keep Pace with an Evolving Threat

Scientists at the University of Pittsburgh School of Medicine are developing a novel coronavirus therapy that they believe has several advantages over existing treatments for the lethal pathogen. The Pitt scientists say their new drug, Ab8, is easier to produce and administer—and more resistant to potential mutations in the virus technically known as SARS-CoV-2—than similar therapies. And, they claim, Ab8 may ultimately be able to both treat and help prevent COVID-19.

There’s a catch, however: Even if Ab8 works like its developers say it could, it may be some time before the drug is available to the public. The Pitt team said it doesn’t expect to begin human trials until next year—even as the president of the United States has made increasingly frantic gestures toward a vaccine possibly being available in a matter of weeks.

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Ab8’s main attribute is its power compared to other drugs, according to John Mellors, chief of the infectious diseases division at Pitt. “Ours is special because it’s extremely potent,” he told The Daily Beast.

Ab8 is a monoclonal antibody drug, meaning it takes advantage of the body’s normal immune functions in order to block or fight a disease. In Ab8’s case, that means adhering to the spike proteins on the SARS-CoV-2 virus and preventing those proteins from attaching to healthy cells.

That’s not unusual. Ab8 “is significant, just not unique,” Pierre Mourad, a University of Washington bio-engineer, told The Daily Beast. “All drugs are trying to attach to some aspect of the virus, or to cells infected by the virus.”

Other coronavirus therapies and vaccine candidates besides Ab8 also seek out the pathogen’s spike proteins, including the leading vaccine candidate from Oxford-AstraZeneca. Development of that vaccine ran into trouble this month after a test subject suffered spinal inflammation during large-scale Phase 3 trials. And as STAT reported, Regeneron Pharmaceuticals and Eli Lilly have been pursuing their own non-vaccine antibody therapies, and appeared to be much further along in the testing process.

A team led by Dimiter Dimitrov, director of Pitt’s Center for Antibody Therapeutics, did the initial research that led to Ab8, using animals as surrogates for human patients. Dimitrov previously developed antibody therapies for the MERS, dengue, Hendra, and Nipah viruses, as well as an older form of SARS, though they did not see widespread use.

Dimitrov’s process was like “panning for gold,” Mellors said. He and the other researchers essentially drew samples from their lab’s vast library of antibodies, created solutions, added bits of the SARS-CoV-2 spike protein, and swirled it all around until antibodies stuck to the proteins.

Dimitrov and his team repeated the process until they’d isolated the smallest possible antibodies that could cover the proteins, they said. They described their results in a Sept. 4 paper in the journal Cell. In the paper, Dimitrov and his co-authors highlighted Ab8’s “potent neutralizing activity,” “specificity” and “good developability properties.”

“It not only reduced the viral load in the lung and alleviated pneumonia, but it also reduced shedding in the upper airway (nasal washes and oral swab), which could potentially reduce transmission of SARS-CoV-2,” Dimitrov and his co-authors wrote.

Thanks to its high potency, Ab8 not only could treat existing COVID cases, it might also help prevent infections in healthy people, Dimitrov and his team argued. 

Another thing that sets Ab8 apart from other monoclonal antibody therapies is that it binds to several parts of the spike protein instead of just one, Mellors explained to reporters at a press conference on Tuesday. That could help Ab8 retain its effectiveness even if the novel coronavirus mutates and the configuration of its spike proteins changes. 

“It is likely that variation of one of those things will not have a negative effect on the antibody,” Mellors said. 

Ab8’s molecules are also smaller than the molecules in similar drugs, he added. 

Stephen Jameson, a University of Minnesota immunologist, told The Daily Beast that, when it comes to monoclonal antibodies, size really does matter. “These small antibody-like molecules may be more effective in therapy,” he told The Daily Beast. 

The small size of the molecules means three things, according to Keith Jerome, a University of Washington virologist. “The fact that it’s so small may allow it to get to sites of infection more easily, and may mean that it would be easier to administer and better tolerated than traditional therapies using the full antibody molecule,” he said.

Indeed, owing to its minuscule dimensions, it may be possible to administer Ab8 in ways other than an injection into a vein, as Mellors explained. He mentioned an inhaler or a subcutaneous injection as possible alternative methods of administration. 

The small size of the molecule also makes Ab8 easier to produce than its competitors, Mellors argued. “We can treat and prevent infection in more people with a set amount of protein, because we need less of it,” he said.

Mourad said he was unsure how quickly the Pitt scientists might be able to move Ab8 through trials and, assuming the U.S. Food and Drug Administration approves it, into production for widespread use. 

Even Mellors was careful to downplay expectations for quick testing and deployment, indicating that Pitt might not even begin human trials until early next year. 

But it’s possible, even very likely, that the demand for better and cheaper COVID therapies will remain strong through 2021. Robert Redfield, director of the U.S. Centers for Disease Control and Prevention, told lawmakers on Wednesday that a coronavirus vaccine might not be widely available to the general public until “the second or third quarter” of next year. 

Hours later, Donald Trump threw cold water on that timeline in his latest fit of vaccine optimism, verging on mania. “When he said it, I believe he was confused,” Trump said of Redfield, adding, “We’re ready to go as soon as the vaccine is approved.”

If nothing else, questions about political manipulation of the vaccine development process have made the need for new, viable therapies, like the ones the scientists at Pitt say they’re developing, clearer than ever.