The U.S. government spent more than $ 18 billion last year funding drug manufacturers to produce a Covid vaccine, an effort that resulted in at least five highly effective vaccinations in record time. Now, more than $ 3 billion is pouring into a neglected area of research: developing pills to fight the virus at an early stage of infection that may save many lives in the years to come.
The new program, announced by the Ministry of Health on Thursday, 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 Pandemic Antiviral Program will also support research into entirely new drugs – not just for the coronavirus, but for viruses that could cause future pandemics.
A number of other viruses, including influenza, HIV, and hepatitis C, can be treated with a simple pill. But despite more than a year of research, there isn’t a pill like this to treat someone with coronavirus infection before it wreaks havoc. Operation Warp Speed, the Trump administration’s program to accelerate Covid-19 research, has invested far more money in vaccine development than in treatments, a void the new program will seek to fill.
Dr. Anthony Fauci, the director of the National Institute of Allergies and Infectious Diseases and a key supporter of the program, said he was looking forward to a time when Covid-19 patients could pick up antiviral pills from a pharmacy once they test positive for that Coronavirus or develop Covid-19 symptoms.
“I wake up in the morning, I don’t feel very well, my sense of smell and taste goes away, I get a sore throat,” said Dr. Fauci 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 fighting AIDS three decades ago. In the 1990s, his institute conducted research that led to some of the first antiviral pills for HIV, “protease inhibitors,” which can block an essential viral protein and keep the virus in check for life.
In the early 2000s, researchers found that an antiviral agent called sofosbuvir could cure hepatitis C nearly 100 percent of the time. Tamiflu, an over-the-counter influenza pill, can reduce recovery time from infection and reduce the chance that a flu attack will bring someone to the hospital.
At the beginning of the pandemic, researchers began testing existing antivirals in people hospitalized with severe Covid-19. But many of these studies showed no benefit from the antiviral drugs. In hindsight, the decision to work in hospitals was a mistake. Scientists now know that the best time to try to block the coronavirus is in the early days of the illness, when the virus is multiplying rapidly and the immune system has not yet built a defense.
Many people fight their infection and recover, but others have immune systems failing and starting to damage tissues instead of viruses. It is this self-inflicted damage that sends many people with Covid-19 to the hospital as the replication of the coronavirus wears off. So a drug that blocks replication early in an infection could very well fail in a study in patients who have advanced into later stages of the disease.
So far, only one antiviral has shown clear benefit for people in hospitals: remdesivir. Originally studied as a potential cure 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 only – antiviral drug to receive full FDA approval for the treatment of the disease.
However, remdesivir’s performance has overwhelmed many researchers. In November, the World Health Organization recommended not using the drug.
Remdesivir could work more effectively if people could take it earlier as a pill in the course of Covid-19. But in its approved formulation, the compound does not act orally. It cannot survive the passage from the mouth via the stomach to the circulatory system.
Researchers around the world are testing other antivirals that are already known to work in tablet form. One such compound called molnupiravir was developed by researchers at Emory University in 2019 and tested against viruses such as influenza and the Venezuelan equine encephalitis virus.
Working with Miami-based Ridgeback Biotherapeutics, the Emory team conducted experiments on mice that were so impressive that Merck turned to them to help bring the drug into human clinical trials for Covid-19.
“We found this molecule really amazing,” said Daria Hazuda, vice president of infectious diseases and vaccine research at Merck.
However, in a study of hospitalized patients, molnupiravir did not appear to have any effect on the disease. In April, the companies announced that they would end the process.
“I see that and I say, ‘Yes, no,'” said Dr. Tim Sheahan, a virologist at the University of North Carolina. “I’m not surprised that these types of drugs would not dramatically improve the outcome of a person who has been sick for several days.”
The companies started a second study last fall, this time testing the drug on people recently diagnosed with Covid-19. This study is ongoing and Merck is recruiting volunteers at higher risk of infection, such as the elderly with obesity and diabetes. Dr. Hazuda said the study should produce clear results by October.
Last year, government funding for Covid-19 treatments focused on a handful of candidates such as monoclonal antibodies and remdesivir. Many other antiviral drug studies have been small and underfunded. In January, the new government of Biden began developing a new program of antiviral pills.
The first results of this planning could be seen last week. The Department of Health and Human Services announced that it will purchase 1.7 million doses of molnupiravir from Merck for $ 1.2 billion, provided the current study leads to Food and Drug Administration approval. According to Dr. David Kessler, the chief science officer of the Biden government’s Covid-19 response team, the government could seek similar deals for two other antivirals in clinical trials.
The hope “is that by the end of the fall we will have an antiviral that can help us close this chapter of the epidemic,” said Dr. Kessler in an interview.
One of the drugs the government is considering is AT-527, which was developed by Atea Pharmaceuticals. The compound has already been shown to be safe and effective for treating hepatitis C, and early studies suggested it could work against Covid-19 as well. 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 government radar was developed by scientists at Pfizer, adapted from a molecule originally developed as a potential drug for SARS in the early 2000s. This drug was on the shelf for years, but last spring scientists decided to change its structure so that it works against the protease of the new coronavirus. More than 200 Pfizer researchers have teamed up to develop the molecule, initially known as PF-07321332.
The drug was intended for intravenous use, but Pfizer researchers managed to modify its structure so that it works as a pill. When the drug was given orally to mice, it reached a concentration high enough in the body to block the coronavirus. Pfizer started a clinical trial in March to evaluate its safety in humans and expects to move to a later stage of testing next month.
Dr. Kessler acknowledged that there will be challenges in using such pills to reduce hospital stays and deaths from Covid-19. People need access to the drugs once they test positive. “Your testing programs need to be linked to your treatment,” he said.
And if the history of antiviral research is any clue, the first drugs for Covid-19 will likely offer only modest benefits against the disease, said Dr. Fauci. But that would be a good start.
“With all of these drugs we’ve looked at over the years, we’ve never landed a home run the first time,” said Dr. Fauci. “A line drive from the left field wall to the start would be really good.”
The government will also spend up to $ 1.2 billion on research centers where scientists will conduct early-stage studies on drugs that block the coronavirus in other ways. Some drugs can interfere with other essential virus proteins, while others make it impossible to copy the virus’ genes.
Even if the next generation of pills won’t hit the market for a few years, many scientists say research will be a good investment. “It could help with this pandemic and potentially be a first line of defense for the next,” said Mark Namchuk, director of therapeutic translation at Harvard Medical School.
The program will not only support research into pills that work against coronaviruses, but also against other high-risk pathogens like flaviviruses, which cause diseases like dengue and West Nile fever, and togaviruses, the mosquito-borne diseases like chikungunya cause and Eastern equine encephalitis.
“There will always be a threat,” said Dr. Fauci. “I think there will be a long-term need for drugs.”
