Stanford’s treatment approach: Hit hard — and early

By Lisa M. Krieger

The Mercury News

Research efforts are laser-focused on finding coronavirus treatments to save the most critically ill.

But what about everyone else?

A new clinical trial at Stanford University is part of an emerging movement to find COVID-19 medicines that can be given almost immediately after infection, before the virus gains a firm foothold in the body.

If effective, this strategy could ease the misery of the estimated 80% of patients who experience mild or moderate symptoms. It might also reduce the risk of progression in the 20% of people at great risk of dangerous disease, and even slow viral spread.

Hopes are pinned on the Stanford outpatient trial of a compound called peginterferon lambda-1a. Already proved safe when tested against other illnesses, it shows early signs of efficacy against the COVID-19 virus in animals.

Stanford is recruiting newly infected people in hopes of reaching 120 volunteers by Memorial Day. Volunteers must be treated within three days of being tested. The drug is given as one shot —less painful than a flu vaccine — which lasts for days. Patients are seen nine times. In addition to Stanford, New York City’s Mount Sinai Medical Center is also conducting a trial.

Currently, the only proven medication for coronavirus — remdesivir — is given intravenously to patients in hospitals after people get sick enough to be admitted. Even then, its benefit is only modest. People still die.

For everyone else, “all we can say is: Please stay home. Self-isolate. Take Tylenol for fever. Drink plenty of fluids. And let us know how you’re doing,” said principal investigator Dr. Upinder Singh, professor of infectious diseases at the Stanford University School of Medicine. Dr. Prasanna Jagannathan, assistant professor of infectious diseases, is also leading the effort.

“Our hope is to identify a compound that we can give to people who are going home, once they’re diagnosed,” she said. “With any infection — whether strep throat, HIV or COVID — earlier treatment is always better.”

The hunt for quick, fast and easy drugs is supported, in part, by the fledgling COVID-19 Early Treatment Fund, created by Silicon Valley tech entrepreneur and medical philanthropist Steve Kirsch.

At 62, Kirsch has diabetes, high blood pressure and is immunocompromised. The Massachusetts Institute of Technology-trained engineer, who has founded seven companies and invented an early version of the optical mouse, cannot risk going out into the world until there are better early treatments, or a vaccine.

“Trump can open up the country as fast as he wants, but I am still locked down,” he said. “If I get the virus, there is nothing proven today to reduce my chance of death. I’d like to be able to go out and do things. But the risk is too great.”

The two-week-old fund, seeded by Kirsch’s $1 million gift and seeking new donors, aims to find the quickest, safest and lowest cost way to repurpose drugs to dramatically reduce hospitalization rates. Its scientific advisory board includes Dr. Robert Siliciano, an immunologist and virologist at Johns Hopkins University; Dr. Rich D’Aquila, an infectious disease expert at Northwestern University and Harvard clinical trials expert Dr. Raj Gandhi.

Dr. Walter Mills, president of the California Academy of Family Physicians, applauded the effort. Family physicians are often the first to see sick patients.

“What if we could treat people on ‘day one,’ when they’re first diagnosed?” said Mills, who is not involved in the Stanford trial. “It would help people get back to work sooner, reduce complications and protect people at high risk.”

The strategy for combating an influenza outbreak sets a good example, he said. Almost immediately after flu is diagnosed in a home or senior living facility, older adults are given the antiviral drug Tamiflu. It may even be given as a prophylaxis, to help prevent illness. Doctors don’t wait for someone to get severely sick to treat them.

“That has saved a lot of lives,” said Mills. “But we have nothing for COVID-19.”

Not yet. The peginterferon lambda-1a compound is an interferon, a family of naturally occurring proteins produced by cells that modulate the response of the immune system to pathogens. This particular drug, made by Eiger Pharmaceuticals, works in the lung epithelial cells and cells of the gastrointestinal tract and liver.

It increases the antiviral activity of these cells, according to Singh. While broad-acting interferon drugs can be dangerous, this one is well-tolerated because it is more targeted.

“If I were sick, this drug would be my first choice,” said Kirsch. “Like a house on fire, the earlier you call, the less damage there is, and the faster the repairs.”

The fund is also supporting research into three other anti-viral compounds, with more candidates in the queue. Until better drugs are discovered, it is focused on “repurposed” drugs that are already approved, because they don’t require Phase 1 safety trials. What needs proof: efficacy.

Favipiravir has been used successfully in China, although it is dangerous in pregnant women, and it is awaiting Food and Drug Administration approval for the first outpatient trials at Stanford and the University of California, San Francisco. Camostat mesylate, used in Japan to treat other illnesses, looks promising in mouse studies.

“For patients, this is a paradigm shift,” said Singh. “At first, we said ‘We don’t have tests, stay home!’ Now we’re saying ‘Get tested, but we can’t do anything.’”

“In this new third stage, there are opportunities,” she said. “We want to know early if you have COVID — because there’s something we can try.”

To donate to the COVID-19 Early Treatment Fund, visit www.treatearly.org.

Stanford University is considering teaching some classes outdoors in tents during the fall as it plans for a partial resumption of campus activity amid the coronavirus pandemic, the school’s provost said. (Dreamstime/TNS)