Coronavirus-onderzoekers maken drugscocktails met Gilead's antivirale remdesivir en tikken op het HIV-playbook om het coronavirus te bestrijdenmei 17, 2020
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- With the antiviral drug remdesivir showing modest benefits for COVID-19 patients, scientists are already plotting how to rapidly build on this progress.
- On its own, remdesivir is unlikely to be a game-changer in treating the coronavirus, researchers said. But finding the right drugs to combine it with could produce a much more potent therapy.
- It is likely to spur a flurry of combination trials that test remdesivir plus additional experimental drugs, leading COVID-19 researchers and physicians said.
- This mirrors the approach used for HIV, where the first drugs showed modest benefits. It took years of testing combinations to find cocktails of two or three drugs that knocked out the virus.
- There’s optimism this testing will happen more quickly than HIV, with many therapeutic candidates already identified.
- Biomedical breakthroughs have built an understanding of the virus in record time, as shown by research published Thursday by a group of more than 100 scientists.
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Researchers are already plotting how to build on top of the first effective coronavirus treatment.
The key will be crafting the right cocktail of medications, testing additional drugs in combination with the antiviral remdesivir, COVID-19 researchers told Business Insider.
This will likely lead to an explosion in combination trials testing Gilead’s treatment in addition to experimental drugs to see if any boosts the benefits. HIV and cancer research have both followed a similar path, providing lessons to guide speedy COVID-19 work.
Hospitalized COVID-19 patients recovered 31% faster when taking remdesivir instead of a placebo, according to preliminary study results released Wednesday by the US National Institutes of Health.
Unlike the majority of early coronavirus studies, this trial’s design was high quality, with data from more than 1,000 patients randomized to receive either Gilead’s drug or a placebo.
That 31% benefit is significant, said Dr. Jeffrey Gold, the chancellor of the University of Nebrasksa’s Medical Center, one of the first hospitals to start testing remdesivir.
Remdesivir’s use should help free up hospital beds, intensive care units, and ventilators as patients recover faster on the drug. But the real advantage will be its potential to serve as a backbone in combination studies, Gold said.
“It’s a very healthy starting point,” Gold said. “It opens the door to multiple combination therapies working in different ways to attack the pandemic, which will hopefully be accelerated.”
The first medications for HIV were single drugs with modest benefits. The real breakthroughs came after years of testing combinations of these drugs, when three-drug cocktails led to dramatic improvements in patients.
“We know clearly, as instructed by the global experience in HIV, that combination therapies often have advantages compared to single-drug therapy,” Dr. Andrew Badley, director of the Mayo Clinic’s HIV Immunology Laboratory, said in an interview.
It won’t be long before researchers start launching trials testing additional therapies on top of remdesivir, he said.
“Those are critical trials, and I think will be coming in the relatively near term,” said Badley, who chairs Mayo’s COVID-19 research task force.
At least one such trial is about to start.
The NIH’s trial will soon start testing a combination therapy, said Dr. Taison Bell, an assistant professor of medicine and infectious disease at the University of Virginia, where he is a principal investigator for this study.
Potentially as soon as next week, patients in the NIH study will all receive remdesivir. They will also be randomized to receive either a placebo or an arthritis drug called Olumiant, Bell said.
Olumiant, made by Eli Lilly, works by interfering with the inflammatory response of the immune system. This could help patients suffering from severe cases of COVID-19, which are often marked by their immune systems overreacting.
The NIH confirmed they are testing Olumiant, but declined to provide specifics on the design. The agency said details would be shared in a future announcement.
Gilead outlined this trial design Thursday on an earnings call, saying the positive trial results for remdesivir will change how COVID-19 drug research is done.
“This now changes the landscape of drug development within COVID-19, being one now has to think about comparing to remdesivir and/or adding to remdesivir,” said CEO Daniel O’Day.
The two drugs work in different ways. Remdesivir is focused on stopping the virus, while Olumiant may help alleviate some of the worst symptoms that patients suffer.
Bell said he is most excited about combination trials where each of the drugs can treat distinct phases of the disease.
“Looking at an agent that tries to attack the virus replication, and then an agent that targets the immune system response when it goes out of whack, looks like that would be the ideal combination for people with severe disease,” Bell said.
Finding the best HIV combinations took years and hundreds, if not thousands of trials, Badley said. But he is optimistic coronavirus research will progress much faster, given recent breakthroughs in biomedical capabilities.
One research project published Thursday in the journal Nature maps a blueprint of how the coronavirus works. An international team of more than 100 researchers identified the dozens of proteins critical to the coronavirus and the hundreds of proteins in humans it needs to grow and replicate.
Then, they found existing drugs that could inhibit these human proteins, hoping that could prevent the virus from growing in cells.
They identified 10 drugs that showed strong ability to inhibit the virus when tested in monkey cells. It’s an eclectic group of compounds, including antihistamines, antipsychotics, and even cancer treatments.
Nevan Krogan, a leader of the project and a biologist at the University of California, San Francisco, said he sees the future of COVID-19 research in “adding multiple drugs like a cocktail.”
“We are excited to be testing our drugs and compounds in combination with each other as well as other antivirals such as remdesivir,” Krogan said.
These drugs hold particular potential to work with remdesivir, since they have different targets that aren’t covered by Gilead’s drug, said UCSF chemist Kevan Shokat, another author of the research.
“In that way, we hit multiple aspects of the viral life cycle all at once,” Shokat said.
Mayo’s Badley said research like this project has identified dozens of drugs that can be repurposed against the coronavirus. It gives him hope the timeline for breakthroughs will be much quicker than HIV.
“The fact that those publications exist is a testament to where we are with biomedical science today,” he said. “We were not in a similar place when HIV came along.”
“I am personally very optimistic that within weeks to months, we will begin to get significant signals of activity of some of these agents as therapies of COVID,” he added.