Opinion | In the Race for a Covid-19 Pill, a Little Lab Plays a Big Role

ATLANTA — Nine years ago, Dr. Dennis Liotta, a professor of organic chemistry at Emory University, set out to change the way drugs are developed for so-called neglected diseases — those that primarily affect populations in poorer countries and for which there exist few, if any, safe and effective treatments.

“The cold hard truth is that it can cost billions of dollars and take decades to develop a new drug,” he said during a TEDx talk in 2016, shortly after the World Health Organization had declared the Zika virus — a neglected disease that had long been overlooked in the African countries where it is endemic — an international public health emergency. “So pharmaceutical companies almost invariably only pursue drugs for diseases that will generate large profits.”

Dr. Liotta would know.

He is a co-inventor of 12 drugs approved by the Food and Drug Administration. Two of them, the antiretrovirals lamivudine and emtricitabine, were instrumental in curbing the spread of H.I.V., the latter having made possible the first-ever combination therapy for the virus in a once-daily pill. Dr. Liotta is considered a leader in discovering new disease-fighting drugs.

Now, many scientists think another drug from Dr. Liotta’s lab could similarly transform the fight against Covid-19.

If approved, Molnupiravir, an antiviral agent licensed by Merck & Co., would be the first treatment for the virus that could be taken as a pill. That would allow it to be quickly and easily disseminated, a major advantage over currently existing options like remdesivir and monoclonal antibody therapies, all of which have to be infused intravenously.

While the F.D.A. is still awaiting data from a Phase II/III clinical trial, Merck says it has partnered with generic drugmakers in India to make Molnupiravir available there pending its authorization for emergency use amid the country’s catastrophic second wave of infections.

Yet even more important than its impact on the current pandemic may be how the antiviral came to be. Molnupiravir may have put Merck back in the lead in the race for a Covid-19 pill, but Merck didn’t invent the drug. That work, the discovery and early development now seldom performed by major drugmakers, was done at DRIVE, the nonprofit Dr. Liotta co-founded in 2012, using royalties from the 2005 sale of emtricitabine (one of the largest-ever intellectual property deals involving a U.S. university).

Short for Drug Innovation Ventures at Emory, DRIVE is one of dozens of university-based drug discovery centers established over the past two decades in response to the dwindling output and rising costs of pharmaceutical research and development.

Supported by government grants, philanthropic gifts and partnerships with industry, these centers have helped stimulate new research. But universities can only take a compound so far. Few have the infrastructure or expertise to advance a promising candidate beyond the earliest stages of discovery. And only pharmaceutical companies have pockets deep enough to put a drug through clinical trials — a risky investment unlikely to be made on anything that isn’t perceived as potentially profitable.

As a result, many projects perish in what scientists call the “valley of death,” the vast gulf between basic discovery and F.D.A. approval.

The problem is bad enough at the best of times: The World Health Organization recently warned that without government intervention, the pipeline for new antibiotics would soon run dry. But it’s especially challenging for pandemic preparedness and response, which requires, in economic terms, “inefficiencies” — among them, investments in research and development around treatments that may never be needed.

“What would someone have paid in July of 2019 for a SARS-CoV-2 drug?” asked Dr. Nat Moorman, a professor of microbiology at the University of North Carolina and director of the Rapidly Emerging Antiviral Drug Discovery Initiative (READDI), a public-private partnership based at U.N.C. “The answer, at the time, would have been, ‘What’s a SARS-CoV-2?’ and ‘nothing,’” he said. “We’re talking about very challenging markets, particularly if you’re looking forward to the next pandemic.”

But in DRIVE, Dr. Liotta and colleagues say they’ve found a way forward, and it’s a model they believe can be replicated.

For one, the group focuses exclusively on the single-stranded RNA viruses responsible for the bulk of the viral disease burden worldwide. “You have to choose an area, and you have to devote all of your personnel, all of your time, all of your resources to that area,” Dr. Liotta told me in 2016. “And what we’d like to do is anticipate where the infectious disease markets of the future are going to emerge.”

As a nonprofit, DRIVE has no shareholders or investors, meaning it can focus on treatments with little or no potential for return on investment. Yet unlike other efforts to develop drugs for neglected diseases, DRIVE doesn’t rely solely on donations. “Philanthropy can help,” said Dr. Liotta, “but with philanthropy alone, it’s very hard to sustain a development process that can last 10 to 12 years.”

Instead, DRIVE pursues a mixed portfolio of major market and neglected diseases, using revenues generated by licensing out the former to subsidize its work on the latter. And it can do that because DRIVE negotiates directly with other companies and institutions, bypassing the layers of bureaucracy typical of academic governance.

“We can’t sell equity, but we can spin out companies, and the money we get from the spinout we put back into the effort,” said DRIVE’s co-founder and chief executive George Painter, a chemist and pharmaceutical industry veteran. It was Dr. Painter who plucked Molnupiravir off the shelf in 2013 (it had been sidelined because of safety concerns) after the Defense Threat Reduction Agency put out a call for a medical countermeasure against Venezuelan equine encephalitis virus (VEEV). Weaponized during the Cold War by both the United States and the Soviet Union, the virus causes swelling of the brain and is considered a possible bioterror threat.

“We figured that if we were to find something for VEEV, it would probably also address other unmet needs, including Eastern equine encephalitis and chikungunya,” said Dr. Painter, referring to a pair of neglected diseases endemic in the Americas. As it turned out, the compound that would become Molnupiravir inhibited those viruses and many more, including Ebola, hepatitis C, seasonal and pandemic influenza and the coronaviruses that cause SARS and MERS. Dr. Painter and his colleagues reported the last results in November of 2019 — just weeks before the news from Wuhan of a mysterious pneumonialike illness.

A decade before they started DRIVE, Dr. Liotta and Dr. Painter teamed up on another venture in South Africa, a start-up called iThemba. The idea had been to license compounds from pharmaceutical companies — those that had shown promise as treatments for a neglected disease but had been abandoned for lack of a financial upside — and, with support from the South African government, conduct the proof-of-principle clinical trials that could move them through the pipeline. At the same time, they would transfer their skills and expertise to the next generation of South African scientists, helping to lay the foundations for a homegrown biotechnology industry.

When promised funding from the government failed to materialize, iThemba was forced to shut down. “That was a hard lesson in the sense that we all invested a lot of ourselves in the company,” Dr. Liotta said. But as a co-founder of Pharmasset, maker of the blockbuster hepatitis C drug sofosbuvir (Sovaldi), he also knew that success could be just as deadly as failure.

In 2011, Pharmasset was acquired by Gilead Sciences for $11.2 billion, and within four months, Dr. Liotta says, “everyone left. They left with a lot of money, but they left. So it’s not the most effective way of having a long-term impact.” At DRIVE, he says, success doesn’t change a thing. “We plow the money back in, we keep the same highly experienced personnel in place, and we move on to the next problem.”

This article is part of Fixes, a series that explores solutions to major social problems. To receive email alerts for Fixes columns, sign up here.

Patrick Adams is a journalist in Atlanta who has written about the pharmaceutical industry.

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