Coronavirus vaccines have reached American adults in record time, but the development of treatments for Covid-19 is stagnating — threatening efforts to stamp out clusters of infection and end the pandemic.

While the Biden administration has committed to channeling billions of dollars into finding therapies, a key government agency that invests in drug development recently stopped reviewing requests for new treatments — in part because it doesn’t have enough cash available, according to one senior health official.

Researchers say the lack of enough drugs for mildly ill patients means that the world may never completely stamp out the virus. “The virus is not going to be eliminated and is now with us forever,” Nigel McMillan, a virologist at Griffith University in Australia, told POLITICO. “It will become like influenza basically.”

The longtime director of the National Institutes of Health, Francis Collins — and other top Biden advisers such as infectious diseases expert Anthony Fauci and David Kessler, who helms the vaccine distribution effort — have made finding effective early Covid-19 therapies a top priority, according to three senior health officials. Advisers to President Joe Biden drafted a $3.2 billion plan during the transition to fund more research, specifically into antiviral treatments that could stem early illness, one of the officials said. The plan was folded into the $1.9 trillion Covid relief package Congress passed this spring.

But effective Covid treatments have proven to be an elusive target. The Health department’s agency to fund early countermeasures, the Biomedical Advanced Research and Development Authority, suspended calls for new therapies in May, partly because of tight budgets that one senior HHS official said could be refreshed with dollars from the American Rescue Plan, H.R. 1319 (117). And past trials yielded mixed results from a number of potential products. BARDA continues to fund nine ongoing projects, eight of which are aimed at more severe Covid cases. Only a single early project for potential antiviral formulas targets mild illness.

There are some therapies available for more common afflictions like seasonal flu. But effective antivirals are hard to find: The ones approved for use aren’t perfect and in some cases are hard to administer. Tamiflu, for example, can only be administered in just the right window to prevent patients from being hospitalized. And the Trump administration’s decision to prioritize Covid vaccine development soon after the coronavirus arrived meant development of new products would slip well past the worst of the pandemic.

Biden intensified the vaccine push within weeks of assuming office. Most of the remaining funding has been allocated for developing drugs for hospitalized and seriously ill patients.

Drugs like the infusion Veklury, also known as remdesivir, are impractical for early interventions when someone may not even be experiencing Covid symptoms: Veklury’s maker Gilead ended a late-stage trial for the medicine in mild-to-moderately ill patients in April, citing low enrollment. Meanwhile, a readily available and cheap steroid, dexamethasone, is only helpful for severely ill patients and may actually cause harm if administered too early.

An HHS spokesperson said the work on Covid therapies is an integral element of the administration’s pandemic response. "We are pulling all levers to accelerate the clinical development and manufacturing of therapeutic candidates most likely to complement the vaccine effort including focusing on antivirals," the spokesperson said.

Fighting the virus would ideally involve patients taking a pill either after they learn they’ve been exposed to the coronavirus or when they’re just beginning to fall ill. That would mimic the approach researchers took during the AIDS crisis and be preferable to using infused or inhaled drugs.

“We’re really putting in a considerable amount of resources in the same approach that we took to the direct acting, antiviral, targeted development of drugs that we did with HIV,” said Fauci, a pioneer in the HIV/AIDS fight.

But antivirals take a long time to perfect — a big reason why the current field is so sparse. Developing the drugs requires a highly specific knowledge of a virus’s biology, which helps them steal the virus’s machinery to make millions of copies of the antiviral agent. Those copies eventually burst from the cell, destroying it, and go on in search of others to infect.

The tricky aspect is making sure that the drug works only in the virus — and doesn’t thwart healthy cells. “It needs to be exquisitely selective for just the target,” Matthew Hall, a biologist at the National Center for Advancing Translational Sciences, told POLITICO.

“It’s highly technical, a small molecular pill. It’s hard to make,” said one senior administration official.

As hospitalizations and deaths spiked early in the pandemic, it made sense for the government to skip over antivirals and focus instead on finding any kind of treatment that could save the lives of those who were severely ill, before scientists knew much about the virus.

It also made sense to avoid developing entirely new drugs, and to instead search for already-approved drugs for other conditions that could be repurposed, or compounds already well along in the development pipeline. That was the case with dexamethasone, a generic steroid, and remdesivir, an antiviral developed to fight other viruses. Both received emergency use authorization from the FDA last year for treating hospitalized Covid-19 patients.

But those therapies weren’t a slam dunk, especially for patients with mild illness. BARDA invested $6 billion in novel therapies targeting SARS-CoV-2 specifically, with most of the money going to large pharmaceutical companies with products already in the pipeline. Most, however, work best with serious infections. Indeed, only one BARDA contract is going toward a therapy that’s more appropriate for people with mild symptoms, and that’s in preclinical studies.

One senior health official believes there’s little incentive to develop new treatments because there’s no market for products that treat people who aren’t bedridden, or worse.

“The coronaviruses that cause common colds don’t make people very ill,” said the NCATS’s Hall. When the SARS pandemic hit in 2001, drug companies expressed short-lived interest in coronavirus antivirals. But as the threat of the virus dimmed, so did drug development. “When SARS went away… there was no disease to develop antivirals against.”

Companies including Pfizer and Merck have revived some of their previous coronavirus antiviral research — though without the government’s help. However, these therapies are in early trials and could be years away from approval, if they’re found to be safe and effective. McMillan, the virologist in Australia, is working on a therapy that is estimated to be ready in 2023.

That leaves a dearth of any early treatments for Covid-19 for now — a situation that some feel could have been avoided. “If the U.S. government and other agencies and pharmaceutical companies kept developing coronavirus therapies after SARS, we would have been in a much better place,” said one senior health official.

While it may be too late to have antivirals on hand for this pandemic, the government could prepare for future ones. Doing so requires working with drug companies before a pandemic starts.

“No pharmaceutical company is going to develop a pandemic preventative therapy off the bat,” a senior health official said.

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