The US government spent more than $18 billion last year funding drugmakers to create a COVID vaccine, an effort that has led to at least five highly effective shots in record time. Now it’s investing more than $3 billion on a neglected area of research: developing pills to fight viruses quickly during infection, potentially saving many lives in the years to come.
new program, announced On Thursday, the Department of Health and Human Services will accelerate clinical trials of some promising drug candidates. If all goes well, some of those first pills could be ready by the end of the year. The Antiviral Program for Pandemic will fully support research on new drugs – not just for the coronavirus, but for viruses that could cause pandemics in the future.
Many other viruses, including influenza, HIV and hepatitis C, can be treated with a simple pill. But despite more than a year of research, no pill exists that can help someone get a coronavirus infection before it wreaks havoc. Operation Warp Speed, the Trump administration’s program to accelerate COVID-19 research, far more money invested in developing vaccines compared to treatment, a gap that the new program will attempt to fill.
Dr Anthony Fauci, director of the National Institute of Allergy and Infectious Diseases and a leading supporter of the program, said he is looking forward to a time when COVID-19 patients can take antiviral pills from a pharmacy as soon as they test positive. For coronavirus or develop COVID-19 symptoms.
“I wake up in the morning, I don’t feel very well, my sense of smell and taste is gone, I have a sore throat,” Dr. Fauci said in an interview. “I call my doctor and say, ‘I have COVID and need a prescription.'”
Dr. Fauci’s support for research on antiviral pills stems from his experience fighting AIDS three decades ago. In the 1990s, his institute conducted research that led to the first antiviral pills for HIV, “protease inhibitors” that block an essential virus protein and can keep the virus at bay for life.
In the early 2000s, researchers found that an antiviral called sofosbuvir could cure hepatitis C about 100 percent of the time. Tamiflu, an over-the-counter pill for influenza, can passing time It helps in recovering from an infection and reduces the chance that a flu outbreak will land someone in the hospital.
Early in the pandemic, researchers began testing existing antivirals in people hospitalized with severe COVID-19. But many of those trials failed to show any benefit from antivirals. In the end, the decision to work in hospitals was a mistake. Scientists now know that the best time to try to stop the coronavirus is in the first few days of illness, when the virus is rapidly replicating and the immune system has yet to defend itself.
Many people recover by crushing their infection, but in others, the immune system fails and the virus begins to damage tissue instead. It is self-inflicted damage that sends many people with COVID-19 to the hospital, as coronavirus replication is decreasing. So a drug that stops replication early in the infection may very well fail trials on patients who have progressed to later stages of the disease.
So far, only one antiviral has shown clear benefit to people in hospitals: remdesivir. Originally investigated as a potential treatment for Ebola, the drug appears to shorten the course of COVID-19 when given intravenously to patients. In October, it became the first – and so far, the only – antiviral drug Full FDA Approval To cure disease.
Remdesivir may work more effectively if people can take it as a pill earlier during COVID-19. But in its accepted formulation, the compound does not work when taken orally. It cannot survive in the passage from the mouth to the stomach to the circulatory system.
Researchers around the world are testing other antivirals that are already known to work in pill form. One such compound, called molnupirvir, was developed in 2019 by researchers at Emory University and has been tested against viruses including influenza and influenza. venezuela equine encephalitis virus.
In partnership with Ridgeback Biotherapeutics of Miami, the Emory team conducted experiments on mice that were so effective that Merck approached them to bring the drug into human clinical trials for COVID-19.
“We thought this molecule was really amazing,” said Daria Hazuda, vice president of infectious disease and vaccine research at Merck.
In a trial in hospitalized patients, however, molanupiravir had no effect on prognosis. In April, companies announced They were quashing the case.
“I look at it, and I’m like, ‘Yeah, no duh,'” said Dr. Tim Sheehan, a virologist at the University of North Carolina. “It doesn’t come as a surprise to me that these types of drugs won’t dramatically improve someone’s outcome when they’ve been sick for several days.”
companies started a second study Last fall, this time drug trials on people recently diagnosed with Covid-19. That trial is ongoing, and Merck is recruiting volunteers at higher risk of infection, such as older people with obesity and diabetes. Dr. Hajooda said the trial would give clear results by October.
Last year, the government focused on a handful of candidates for COVID-19 treatment, such as monoclonal antibodies and remdesivir. There were many other studies on antivirals small and underfunded. In January, the impending Biden administration began rolling out a new program dedicated to antiviral pills.
Last week saw the first results of this scheme. Department of Health and Human Services announced That it will purchase 1.7 million doses of mollupiravir from Merck at a cost of $1.2 billion, provided that current trials lead to authorization by the Food and Drug Administration. The government may seek similar deals for two other antivirals in clinical trials, according to Dr David Kessler, chief science officer of the Biden administration’s COVID-19 response team.
The hope “is that we can have an antiviral by the end of the fall that can help us close this chapter of the pandemic,” said Dr. Kessler said in an interview.
One of the drugs the government is considering is AT-527, Developed by Atia Pharmaceuticals. The compound has already been proven to be safe and effective as a treatment for hepatitis C, and early studies suggested it may also work against COVID-19. Roche has partnered with Aetia to test it in people, and the companies are currently running a late clinical trial.
The second drug on the government’s radar was created by scientists at Pfizer, adapted from a molecule initially designed in the early 2000s as a potential drug for SARS. That drug had been lying on the shelf for years, but last spring, scientists decided to modify its structure so that it worked against the new coronavirus’s protease. More than 200 Pfizer researchers joined the effort on the molecule, now known as PF-07321332.
The drug was designed to be taken intravenously, but researchers at Pfizer succeeded in changing its structure to work as a pill. When rats The drug was given orally, until it reached levels high enough in the body to block the coronavirus. pfizer launched A clinical trial in March to study its safety in people, and is expected to move to a later-stage trial next month.
Dr. Kessler acknowledged that there would be challenges in using such pills to reduce hospitalizations and deaths from COVID-19. People will need to gain access to medicines as soon as they test positive. “Your testing programs have to be linked to your treatment,” he said.
And if the history of antiviral research is any guide, the first drugs for COVID-19 will probably only provide a modest benefit against the disease, Dr. Fauci said. But it would be a good start.
“With all these drugs we’ve dealt with over the years, we’ve never hit a home run to bat first,” said Dr Fauci. “A line drive from the left field wall to start would be really nice.”
The government will spend up to $1.2 billion on research centers where scientists will conduct early-stage studies on drugs that can prevent the coronavirus by other means. Some drugs can interfere with other essential viral proteins, while others can make it impossible for the virus’s genes to be copied.
Even if the next generation of tablets doesn’t arrive for a few years, many scientists say the research will be a good investment. “It could help with this pandemic and potentially provide the first line of defense for the next one,” said Mark Namchuk, director of therapeutic translation at Harvard Medical School.
The program will support research not only on pills that work against the coronavirus, but also against other high-risk pathogens, such as flaviviruses, which cause diseases such as dengue fever and West Nile fever, and togavirus, which Causes mosquito-borne diseases like Chikungunya. and Eastern equine encephalitis.
“There will always be a danger,” Dr. Fauci said. “I think there will be a need for long-range drugs.”