An experimental drug used to treat strokes could also help treat COVID-19, researchers and the drug’s manufacturer claim.
The drug TXA127 works by replacing a key lung enzyme that the novel coronavirus has a tendency to suppress. There’s some evidence that this replacement enzyme could help to calm the overactive immune response—the so-called cytokine storm—that’s common in severe COVID cases.
But it’s too soon to say for sure. The Food and Drug Administration hasn’t approved TXA127 for use on people. The first major clinical trial of the drug is just getting organized at Columbia University in New York.
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Still, Rick Franklin, the CEO of Boston-based Constant Therapeutics, is optimistic. “It is an extremely strong theory that this drug ought to work,” Franklin told The Daily Beast.
One of the most dangerous things about the SARS-CoV-2 virus isn’t the virus itself, it’s the response the pathogen can provoke from an infected person’s immune system.
In many patients, their immune systems detect the novel coronavirus and produce an overabundance of cytokines, which are chemicals that guide a healthy immune response.
Stoked by the “cytokine storm,” immune cells might attack not only the virus but healthy tissues as well. That can lead to catastrophic organ failure.
For months, doctors all over the world have scrambled to identify drugs, or a mix of drugs, that can calm the cytokine storm. Tocilizumab is one strong candidate, as are sarilumab and anakinra.
Franklin said he and his colleagues at Constant Therapeutics believe TXA127 could work, too. “We think it’s very likely.”
Franklin has described TXA127 as a “missing piece” in the COVID puzzle. Doctors already plan to prevent SARS-CoV-2 infections with vaccines or, failing that, directly attack the virus using antiviral drugs. TXA127, by contrast, is defensive rather than offensive. Where antivirals attack the pathogen, Franklin’s drug protects the patient’s own tissue.
TXA127 is an artificial version of the angiotensin-1-7 enzyme that occurs naturally in a healthy human body. Angiotensin-1-7 is a protective molecule. It stops other molecules from infiltrating lung tissue via the tissue’s AT1 receptors and causing inflammation.
But here’s the catch: Angiotensin-1-7 is produced by the ACE2 receptor, which is also the novel coronavirus’ favorite receptor for entering the lungs. When the pathogen attacks, it stops ACE2 receptors from producing angiotensin-1-7. “In effect, you’re getting an angiotensin-1-7 deficiency,” Franklin explained.
An injection of a “receptor-blocker” such as TXA127 could alleviate that deficiency, according to a study by Spanish scientists Concepción Peiró and Salvador Moncada that appeared in the journal Circulation in April. “Using AT1 receptor blockers might protect against viral-induced lung injury,” Peiró and Moncada wrote.
“It didn’t take a genius for us to realize all you should have to do is give back that which has been lost,” Franklin said.
Constant Therapeutics is a small firm with just three employees and $25 million in private start-up capital. Its original goal was to develop TXA127 to treat stroke victims. The pandemic compelled the company to reconsider its strategy, Franklin said. “Starting in early April, we had six or eight unsolicited requests to us [asking] would we supply the drug for clinical trials.”
The company has teamed up with Columbia University for the first major trial of TXA127 for treating COVID patients. That phase two trial, led by Columbia lung researcher Jeanine D’Armiento, just began recruiting its first 100 test subjects. D’Armiento didn’t respond to an email seeking comment.
The Columbia trial is double-blinded, placebo-controlled, and randomized. It’s slated to begin this month and end in one year, according to the FDA’s online trial tracker. Results could be available as early as December 2021.
If TXA127 passes its COVID trials, Constant Therapeutics could ramp up production of the drug, Franklin said. “It’s straightforward to manufacture.”
But that requires cash, he stressed. “Getting the funding for large-scale production, the way there is for all of the vaccines in development, is impossible for us,” he said.
Keith Jerome, director of the University of Washington’s virology lab, said he’s intrigued by TXA127’s potential to settle the cytokine storm. “It’s a fascinating hypothesis,” Jerome said, “and since the drug is essentially acting on the host rather than the virus, it’s possible that it might work well in combination with antivirals.”
