As the world scrambles to find antiviral treatments and vaccines for the novel coronavirus, some scientists are looking ahead to a problem on the horizon: Many Covid-19 survivors will have long-term lung injuries, and medicine has little to offer them.
There’s only scant data on how many patients who recover from Covid-19 are left with long-term fibrosis, or scarring of the lung. But studies on SARS and MERS, relatives of the novel coronavirus, suggest about 30% of patients had signs of fibrotic lung disease months after recovery. And, considering the novel coronavirus has already infected more than 5 million people worldwide, debilitating lung problems could become a global scourge.
PureTech Health, a biotech company in Boston, believes it might have a solution after making some chemical alterations to an older drug that has helped prevent scarring in a different lung disease. The reference treatment, pirfenidone, works by blocking the proteins that lead to fibrosis, but there’s evidence it can also tamp down inflammation. For Covid-19, where lung injury is caused by severe immune reactions, that could be a beneficial combination, said Sakshi Dua, a pulmonologist and professor at the Icahn School of Medicine at Mount Sinai.
“Intuitively, this makes a lot of medical and scientific sense,” said Dua, who isn’t involved with PureTech. “Pirfenidone is a very peculiar, fascinating molecule in its ability to affect various different chemical pathways in the lung.”
It also requires patients to take nine pills a day and has well-documented side effects, including liver toxicity, nausea, and diarrhea. With those issues in mind, PureTech tinkered with pirfenidone’s hydrogen atoms through a process called deuteration, which gives molecules a longer half-life and more durable effect. The resulting drug, LYT-100, should be more tolerable than pirfenidone, said Eric Elenko, PureTech’s chief innovation officer, but still preserve the original medicine’s benefits for fibrosis and inflammation.
In the third quarter, PureTech plans to test its theory. The company will enroll about 150 patients who have respiratory problems related to Covid-19 but don’t require ventilation. Participants will get either LYT-100 or placebo, and PureTech will measure whether the drug improved lung function after up to three months of treatment. The company expects to have data in mid-2021.
Whether LYT-100 can do for Covid-19 what pirfenidone has done for other lung diseases remains an open question. Pirfenidone is effective in slowing down or halting the process of fibrosis, but there’s no evidence to show it reverses existing scarring, said Teng Moua, a pulmonologist at Mayo Clinic. That means LYT-100, in order to make a difference, will have to thread the needle with Covid-19, reaching patients before they develop irreversible damage.
But that approach creates a challenge, said Dan Culver, a pulmonologist at the Cleveland Clinic. PureTech is targeting patients whose Covid-19 isn’t severe enough to require ventilation. In order for LYT-100 to demonstrate a benefit, a significant number of patients on placebo need to develop fibrosis. There’s not enough data on Covid-19 to guarantee that’ll happen, Culver said.
“I wonder how easy it will be to see a signal with that sort of group,” he said. “It’s possible, but from what I know, I’m not sure I can say that that’s going to be realistic.”
Ideally, doctors could determine beforehand which Covid-19 cases were most likely to lead to fibrosis, but “the only way to do that is if you had a reliable biomarker or some way to predict who those patients are,” said Rany Condos, a pulmonologist at NYU Langone Health. “And we don’t really have that yet.”
PureTech believes LYT-100 could be a step forward, addressing Covid-19’s intertwining effects on the immune system and the lungs. And if everything works out, it could be a useful medicine for the next phase of the coronavirus pandemic, in which the world deals with the medical aftermath of Covid-19.
“Once we get through the initial flurry of keeping people alive, the question becomes are there long-term effects we should be considering,” said Dennis Ausiello, the former chief of medicine at Massachusetts General Hospital and current member of PureTech’s scientific advisory committee. “What we don’t want to end up with is a population of patients who survived Covid-19 but end up with 30, 40, 50% lung impairments going forward.”