Can daily pills treat COVID-19 right after diagnosis? Research in Seattle may have answer within months

Within a day of testing positive for COVID-19 in June, Miranda Kelly was sick enough to be scared. At 44, with diabetes and high blood pressure, Kelly, a certified nursing assistant, had difficulty breathing and symptoms were severe enough to send her to the emergency room.

When her husband Joe, 46, got the virus, she became very concerned, especially about her five teenagers at home: “I thought, ‘I hope to God we don’t end up on ventilators. We have children. Who will raise these children? ‘”

But the Kellys, who live in Seattle, soon after their diagnosis agreed to take part in a clinical trial at the nearby Fred Hutchinson Cancer Research Center, part of an international effort to test an antiviral treatment that could treat COVID-19 early could stop.

The next day, the couple took four pills twice a day. Although they weren’t told whether they were given an active drug or a placebo, they said their symptoms were better within a week. They recovered within two weeks.

“I don’t know if we got the treatment, but I feel like we have,” said Miranda Kelly. “In order to have all these framework conditions, I had the feeling that the recovery was very quick.”

The Kellys play a role in developing the world’s next chance to thwart COVID-19: taking short-term daily pills that can fight the virus early after diagnosis and potentially prevent symptoms from developing after exposure.

“Oral antivirals have the potential not only to shorten the duration of COVID-19 syndrome, but also to limit transmission to people in your household when they’re sick,” said Timothy Sheahan, a virologist at the University of North Carolina -Chapel Hill for helping advance these therapies.

Antivirals are already essential treatments for other viral infections, including hepatitis C and HIV. One of the best known is Tamiflu, the widely prescribed pill that, when given quickly, can shorten the duration of the flu and reduce the risk of hospitalization.

The drugs developed to treat and prevent viral infections in humans and animals work differently depending on the type. But they can be designed to boost the immune system, fight infections, block receptors to keep viruses from entering healthy cells, or reduce the amount of active viruses in the body.

At least three promising antivirals for COVID-19 are being tested in clinical trials, with results expected as early as late fall or winter, said Carl Dieffenbach, director of the AIDS division at the National Institute of Allergy and Infectious Diseases, who oversees antiviral development .

“I think that in the next few months we will have answers about what these pills can do,” said Dieffenbach.

The lead candidate is a drug from Merck & Co. and Ridgeback Biotherapeutics called molnupiravir, Dieffenbach said. This is the product being tested in the Kellys’ Seattle study. Two more are a candidate from Pfizer, known as PF-07321332, and AT-527, an antiviral agent manufactured by Roche and Atea Pharmaceuticals.

They work by interfering with the virus’ ability to replicate in human cells. In the case of molnupiravir, the enzyme that copies the genetic material of the virus has to make so many mistakes that the virus cannot multiply. This in turn reduces the patient’s viral load, shortens the infection time and prevents dangerous immune reactions that can lead to serious illness or death.

So far, only one antiviral drug, remdesivir, has been approved for the treatment of COVID-19. However, it is given intravenously to patients sick enough to be hospitalized and is not intended for early, widespread use. In contrast, the top contenders being studied can be packaged as pills.

Sheahan, who also did preclinical work on remdesivir, led an early study in mice that showed molnupiravir could prevent early disease from SARS-CoV-2, the virus that causes COVID-19. The formula was discovered at Emory University and later acquired by Ridgeback and Merck.

Clinical studies followed, including an early study of 202 participants last spring that showed that molnupiravir rapidly lowered levels of the infectious virus. Robert Davis, CEO of Merck, said this month that the company is expecting data from its larger Phase 3 trials in the coming weeks, with the option to apply for emergency approval with the Food and Drug Administration “before the end of the year.” .

Pfizer started a combined phase 2 and phase 3 study of its product on September 1, and Atea officials said they expect results from phase 2 and phase 3 studies later this year.

If the results are positive and an emergency application is granted for a product, Dieffenbach said, “sales could begin quickly.”

That would mean millions of Americans could soon have access to a daily oral drug, ideally a single pill, which could be taken for five to ten days at the first confirmation of COVID-19 infection.

“When we get there, that’s the idea,” said Dr. Daniel Griffin, an infectious disease and immunology expert at Columbia University. “To have this across the country so people can get it the same day they’re diagnosed.”

Once marginalized for lack of interest, oral antivirals used to treat coronavirus infections are now the subject of stiff competition and funding. In June, the Biden government announced that it had agreed to receive approximately 1.7 million courses of treatment of Merck’s molnupiravir at a cost of $ 1.2 billion if the product receives emergency approval or full approval. In the same month, the government announced it would invest $ 3.2 billion in the pandemic antiviral program, which aims to develop antivirals for the COVID-19 crisis and beyond, Dieffenbach said.

The pandemic has started a long-neglected attempt to develop effective antiviral treatments for coronavirus, Sheahan said. Although the original SARS virus scared scientists in 2003 – followed by the Middle East Respiratory Syndrome or MERS in 2012 – research slowed when these outbreaks did not persist.

“The commercial drive to develop products has simply stalled,” Sheahan said.

Widely used antiviral drugs would complement the monoclonal antibody therapies already used to treat and prevent serious illness and hospitalization caused by COVID-19. The laboratory-made monoclonal antibodies, which mimic the body’s natural response to infection, were easier to develop but must be administered primarily through intravenous infusions.

The federal government covers the cost of most monoclonal products at $ 2,000 per dose. It’s too early to know how to compare the price of antiviral drugs.

Like the monoclonal antibodies, antiviral pills would not be a substitute for vaccination, Griffin said. They would be another tool to fight COVID-19. “It’s nice to have another option,” he said.

One of the challenges in the rapid development of antiviral drugs has been to recruit enough participants for the clinical trials that will involve many hundreds of people, said Dr. Elizabeth Duke, a research assistant to Fred Hutch who is overseeing the molnupiravir study.

Participants must be unvaccinated and enrolled in the study within five days of a positive COVID-19 test. Every day interns make 100 calls to new COVID-positive people in the Seattle area – and most of them say no.

“Just in general there is a lot of suspicion about the scientific process,” said Duke. “And some people say pretty bad things to interns.”

If the antiviral pills prove effective, the next challenge is to build a distribution system that can get them to people once they test positive. Griffin said it would take something similar to the program set up by UnitedHealthcare last year that sent Tamiflu kits to 200,000 high-risk patients enrolled in the insurer’s Medicare Advantage plans.

Merck officials predicted the company could produce more than 10 million courses of therapy by the end of the year. Atea and Pfizer did not publish similar estimates.

Even more promising? Studies to determine whether antivirals can prevent infection after exposure.

“Think about it,” said Duke, who is also overseeing a prophylactic study. “You could give it to everyone in a household or to everyone in a school. Then we talk about a return to maybe normal life. “

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KHN (Kaiser Health News) is a national newsroom that produces in-depth journalism on health topics. Together with Policy Analysis and Polling, KHN is one of the three major operational programs of the KFF (Kaiser Family Foundation). KFF is a non-profit foundation that provides the country with information on health issues.