The U.S. government will invest $ 3.2 billion to develop antiviral pills for Covid-19, the Department of Health and Human Services announced Thursday. Such treatment could keep people out of the hospital and possibly save lives in the coming years, as the virus becomes a permanent threat despite the spread of effective vaccines.
A number of other viruses, including flu, HIV and hepatitis C, can be treated with a simple pill. But despite more than a year of research, there is no such cure for the coronavirus. Operation Warp Speed, the Trump administration’s program to accelerate Covid-19 research, has invested far more money in vaccine development than for treatments, a gap the new program will seek to fill.
The new influx of money will speed up the clinical trials of some promising drug candidates. If all goes well, some of the pills may be available by the end of this year. The antiviral program for pandemics will also support research on completely new drugs – not only for the coronavirus, but also for viruses that can cause future pandemics.
Dr. Anthony Fauci, director of the National Institute of Allergy and Infectious Diseases and a key pillar of the program, said he was looking forward to a time when Covid-19 patients could pick up antiviral pills at a pharmacy once they tested positive has. for the coronavirus or develop Covid-19 symptoms.
“I wake up in the morning, I do not feel very well, my sense of smell and taste disappear, I have a sore throat,” said Dr. Fauci said in an interview. “I call my doctor and say, ‘I have Covid and I need a prescription. ”
Dr. Fauci’s support for antiviral pill research stems from his own experience in the fight against 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 alive.
In the early 2000s, researchers found that an antiviral drug called sofosbuvir hepatitis C could cure almost 100 percent of the time. Tamiflu, an over-the-counter pill for flu, can cut the time it takes to recover from an infection and reduce the chance that a flu attack will land someone in the hospital.
At the onset of the pandemic, researchers began testing existing antiviral drugs in people hospitalized with severe Covid-19. But many of these trials showed no benefit from the antiviral drugs. In retrospect, the choice to work in hospitals was a mistake. Scientists now know that the best time to try to block the coronavirus is in the first few days of the disease, when the virus recovers rapidly and the immune system does not yet have a defense.
Many people crush their infection and recover, but in others the immune system misses out and starts damaging tissues instead of viruses. It is this self-inflicted damage that many people with Covid-19 send to hospital as coronavirus replication decreases. Thus, a drug that blocks replication early in an infection may well fail in a trial on patients who have progressed to the later stages of the disease.
So far, only one antiviral drug has shown a clear benefit for people in hospitals: remdesivir. Originally investigated as a possible drug for Ebola, the drug appears to shorten the course of Covid-19 when given intravenously to patients. In October, it was the first – and so far the only – antiviral drug approved by the FDA to treat the disease.
Yet remdesivir’s performance has undercut many researchers. In November, the World Health Organization recommended that the drug not be used.
Remdesivir may work more effectively if humans could take it as a pill earlier in the course of Covid-19. But in the approved formulation, the compound does not work orally. It cannot survive the transition from the mouth to the stomach to the bloodstream.
Researchers from around the world are testing other antiviral drugs that are already known to work in pill form. One such compound, called molnupiravir, was develop in 2003 by researchers at Emory University and was tested against viruses, including influenza and dengue.
In collaboration with Ridgeback Biotherapeutics of Miami, the Emory team performed experiments in mice that were so impressive 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.
However, in a trial of hospitalized patients, it appears that molnupiravir has no effect on the disease. In April, the companies announced they canceled the trial.
“I see it, and I’m like, ‘Yeah, no duh,’” said Dr. Tim Sheahan, a virologist at the University of North Carolina. “It is not surprising to me that such drugs would not make a dramatic improvement in someone’s outcome if they had been ill for several days.”
The companies started a second study last fall, this drug was tested this time on people recently diagnosed with Covid-19. The trial continues and Merck is recruiting volunteers at higher risk for infection, such as older people with obesity and diabetes. Dr. Hazuda said the trial should yield clear results by October.
Last year, the government’s funding of Covid-19 treatments focused on a handful of candidates, such as monoclonal antibodies and inhibitors. Many other studies on antiviral drugs were small and underfunded. In January, the incoming Biden administration began designing a new program dedicated to antiviral pills.
Last week, the first results of this planning took place. The Department of Health and Human Services announced that it would buy 1.7 million doses of molnupiravir from Merck for $ 1.2 billion, provided the current trial leads to authorization by the Food and Drug Administration. According to David Kessler, chief scientific officer of the Biden administration’s Covid-19 response team, the government may seek similar agreements for two other antiviral drugs in clinical trials.
The hope ‘is that by the end of the autumn we can find an antiviral remedy that can help us close this chapter of the epidemic’, said dr. Kessler said in an interview.
One of the remedies the government is considering is AT-527, developed by Atea Pharmaceuticals. The compound is already safe and effective as a treatment for hepatitis C, and early studies have suggested that it may also work against Covid-19. Roche has partnered with Atea to test it in humans, and the companies are currently conducting a late-stage clinical trial.
The other drug on the government’s radar was created by Pfizer scientists, adapted from a molecule initially designed in the early 2000s as a potential drug for SARS. The drug has been on the shelf for years, but scientists decided last year to change its structure so that it could work against the protease of the new coronavirus. More than 200 Pfizer researchers have joined forces over the attempt at the molecule, formerly known as PF-07321332.
The medicine was designed to be taken intravenously, but the Pfizer researchers succeeded in changing the structure to act as a pill. When mouse the medicine was administered orally, it reached high enough levels in the body to block the coronavirus. Pfizer launched a clinical trial in March to study its safety in humans, and expects to go test to later stages next month.
Dr. Kessler acknowledged that there would be challenges in using such pills to ward off hospitalizations and deaths due to Covid-19. People will need to access the drug as soon as it is positive. “Your testing programs will need to be linked to your treatment,” he said.
And if the history of antiviral research is a guideline, the first drugs for Covid-19 are likely to offer only modest benefit against the disease, Drs. Fauci said. But that would be a good start.
“With all of this medicine that we have been dealing with over the years, we have never been on the run for the first time,” said Dr. Fauci said. A line ride from the wall of the left field to start would be really good. ‘
The government will also spend up to $ 1.2 billion on research centers where scientists will conduct early studies on drugs that block the coronavirus in other ways. Some drugs may interfere with other essential viral proteins, while others may make it impossible to copy the virus’ genes.
Even if the next generation of pills does not come for a few years, many scientists say that the research will be a good investment. “It could help with this pandemic and could potentially provide a first line of defense for the next one,” said Mark Namchuk, director of therapeutic translation at Harvard Medical School.
The program supports not only research on pills that work against coronaviruses, but also against other high-risk pathogens, such as flaviviruses, which cause diseases such as dengue fever and West Nile fever, and togaviruses that cause mosquito-borne diseases such as chikungunya. and eastern equine encephalitis.
“There will always be a threat,” said Dr. Fauci said. “I think there’s going to be a long-term need for drugs.”
picture By KamranAydinovStudio