Researchers at UCSF have begun testing a mixture of two of the most promising treatments for COVID-19 in hopes that the concoction will be the “golden ticket” everyone is looking for to neutralize the coronavirus and relieve world anxiety.
Doctors conducting the study, which is sponsored by the National Institutes of Health, treated their first patient last week with a combination of remdesivir, an antiviral drug developed to treat Ebola, and interferon, an anti-inflammatory used for people with multiple sclerosis.
The hope is that, together, the two drugs will cut the length and severity of sickness and reduce the number of deaths caused by SARS-CoV-2, the specific coronavirus that causes COVID-19.
“We are looking for the golden ticket,” said Peter Chin-Hong, a professor of medicine and infectious diseases at UCSF, who is on the study team. “The gold medalist will be a combination of drugs that will get you to the sweet spot.”
It is the third phase of NIH-sponsored drug trials looking for a medicinal cocktail, like the combination of treatments HIV-AIDS patients now use to control infection. Researchers hope to develop an effective drug cocktail for COVID-19 by the end of the year.
Remdesivir, which is made by Gilead Sciences of Foster City, interferes with the process through which the coronavirus replicates itself. A large study led by the federal government generated excitement in late April when hospitalized patients who received remdesivir intravenously recovered faster than those who received a placebo.
Doctors have been using remdesivir to treat severely ill patients ever since. The problem is that there is conflicting evidence on whether remdesivir reduces the number of deaths, so “it’s not a gold medalist in my Olympics of drugs,” Chin-Hong said. “It’s a silver medalist.”
That is where beta interferon comes in, he said. A recent study in the United Kingdom showed hospitalized people who inhaled interferon like an asthma medication recovered faster. He said the preliminary study, which has not yet been peer reviewed, showed an 80% decrease in both fatalities and the number of patients on breathing tubes compared to people on a placebo.
Interferon has also reportedly worked in laboratory studies on SARS, a coronavirus identified in 2003 in China, and MERS, discovered in Saudi Arabia in 2012. Those viral respiratory illnesses caused similar symptoms to those in people infected by SARS-CoV-2.
An added benefit, Chin-Hong said, is that interferon is readily available, relatively cheap and can be given to patients at home.
“That’s why interferon is the darling right now,” he said.
The plan is to enroll patients at UCSF and some 100 other places around the world. The 1,000 or so patients in the study will all be given a remdesivir infusion. Half will also be injected with interferon, while the other half will get a placebo. The researchers will then study how the patients in each group react over time.
The combination is necessary, Chin-Hong said, because remdesivir is designed to attack the virus, while interferon reduces inflammation. The inflammatory response, known as a cytokine storm, is a serious problem among COVID-19 patients whose immune systems overreact to the disease, worsening infections in the lungs and other organs.
If the two drugs work well together, researchers think they could use it as an outpatient treatment that might prevent hospitalizations. Gilead Sciences is studying a nebulized formula of remdesivir that could be inhaled at home.
“It would mean I have something I can give patients that would decrease hospitalizations, decrease deaths and decrease the need for a breathing tube,” Chin-Hong said. “All those things would make me feel excited.”
Art Reingold, a professor of epidemiology at the School of Public Health at UC Berkeley and unaffiliated with the study, cautioned against getting one’s hopes up too high.
“It will be nice if it works,” Reingold said. “But many things don’t.”
John Swartzberg, an infectious disease expert at the UC Berkeley School of Public Health, also downplayed the potential benefits of the two-drug combination. It is “perhaps a beacon of hope for those who are very ill from COVID-19, (but) this is certainly not a game-changer,” he said. “What we need is something at the other end of COVID-19’s spectrum: an oral med taken at the first signs of illness or after exposure. That would be a game-changer!”
The two drugs aren’t the only ones that have shown promise. The steroid dexamethasone significantly reduced fatalities in seriously ill COVID-19 patients during a recent drug trial conducted by the University of Oxford. That finding marked the first time any coronavirus treatment has proven to prevent deaths.
Chin-Hong said remdesivir, dexamethasone and other treatments and techniques developed during the pandemic have already reduced deaths in hospitals around the country, offering hope and an incentive to intensify the search for more effective treatments.