A closely watched clinical trial showed Wednesday that remdesivir, an experimental antiviral therapy developed by Gilead, could help patients hospitalized with COVID-19, a result that puts the drug center stage in a global push to find treatments for the infectious disease.
"We really did need a win," said Taison Bell, an assistant professor of medicine and infectious disease doctor at the University of Virginia, in an interview. Bell called the study the "first high-quality trial to demonstrate efficacy for a therapeutic agent" against the disease.
Anthony Fauci, director of the National Institute for Allergy and Infectious Diseases, said in remarks at the White House Wednesday that remdesivir doesn't look like a "knockout," but that the results are a "very important proof of concept."
The study, which enrolled more than 1,000 patients at hospitals in 19 states and nine foreign countries, showed treatment with remdesivir led to faster recovery than did placebo, according to NIAID, the clinical trial's sponsor.
No drugs have been shown to be clearly effective in treating COVID-19, which has led to the deaths of nearly 230,000 people worldwide. The desperate urgency of the pandemic has greatly raised the stakes of drug development, and increased the risk that initial signs of a treatment's effectiveness could be overstated in hopes of rushing therapies to the frontlines of the crisis.
Physicians and experts interviewed by BioPharma Dive regard the NIAID study as the most definitive test of remdesivir's potential, in large part because it compared the drug's effect against a placebo. A trial run by Gilead in patients with severe COVID-19, results of which were also disclosed Wednesday, lacked a control group and were therefore more difficult to assess on their own.
In the NIAID study, the median time to recovery for patients given remdesivir was 11 days, compared with 15 days for those who received placebo. Fewer patients on treatment died, as well, although the difference versus the number of deaths in the control group was not large enough to be considered statistically significant.
While remdesivir's benefit looks modest, the data are the strongest sign yet that an antiviral treatment can ease COVID-19's symptoms and, potentially, the burden on hospitals stretched to the breaking point in the U.S. and elsewhere. And, as remdesivir wasn't originally designed to go after the new coronavirus, its qualified success bolsters confidence that other, purpose-built therapies in development could be more effective.
"A day less in the hospital is a lot of resources saved in terms of our staffing, your physical space and your PPE," said UVA's Bell, referring to personal protective equipment. UVA is a site for the NIAID trial.
Neera Ahuja, a division chief of hospital medicine at Stanford University School of Medicine, called the four-day difference "quite meaningful" in an email to BioPharma Dive. Stanford is also a trial site.
Detailed data from the NIAID weren't immediately available, so it's not yet clear which patients experienced the most benefit observed in the study.
If patients who needed intensive care, or mechanical ventilation, improved the most, that could make a significant difference for hospitals, said Cameron Wolfe, an associate professor of medicine at Duke University School of Medicine and a principal investigator for the NIAID study there, in an interview.
The results, however, don't show remdesivir to be a home-run treatment, or anything close.
"This is not giving penicillin to someone who has syphilis," said Wolfe. "This is an antiviral drug, and the history of respiratory viral drugs is they often have subtle benefits and rarely huge swings in mortality benefit."
A smaller trial in China, published Wednesday in The Lancet, found no benefit to remdesivir versus placebo. But low enrollment caused investigators to stop the study early, which confounded statistical comparisons between the two groups.
Still, the Food and Drug Administration will be under pressure to quickly expand access to remdesivir, and could soon clear the drug for emergency use, according to reports in The New York Times and The Wall Street Journal.
"I want them to go as quickly as they can," said President Donald Trump at an event Wednesday, referring to the drug agency. "We want everything to be safe. But we would like to see very quick approvals, especially with things that work."
In a statement, the FDA said it has been "engaged in sustained and ongoing discussions with Gilead regarding making remdesivir available to patients as quickly as possible, as appropriate."
In March, the FDA granted an emergency authorization to two versions of hydroxychloroquine, the malaria pill controversially touted by President Trump as a potentially effective treatment for COVID-19 on thin evidence.
Hydroxychloroquine's rise as one of the most discussed potential therapies for COVID-19 was surprising, as it's not clear why the drug and its related variants would work against the disease. Remdesivir, though, has a better understood mechanism by which it disrupts the viral cause of COVID-19, which led to initial enthusiasm for its potential.
"There's a really sound scientific hypothesis behind why it could have efficacy," said Jen Heemstra, an associate professor of chemistry at Emory University, in an interview conducted before data on the drug were disclosed. "Compared to hydroxychloroquine or chloroquine — it's a lot less obvious why those would work."
Both hydroxychloroquine and remdesivir have been proposed as antiviral therapies for past infectious disease outbreaks, such as Ebola, only for subsequent testing to diminish their prospects.
Remdesivir is thought to stop SARS-CoV-2, as the new coronavirus is called, from reproducing itself in cells it's invaded, a mechanism of action that suggests giving it sooner in the course of disease could help patients more.
Some signs from Gilead's trial, as well as the study in China that was halted early, support that thinking, although the data aren't conclusive.
In its study, Gilead compared five days of remdesivir treatment to 10 days in patients with severe disease, a design that drew criticism but was meant to answer questions about how best to use the drug clinically. Patients appeared to do equally well on either regimen, showing signs of improvement in either 10 or 11 days — a result that matches with the NIH's findings and suggests there's no need to give remdesivir for longer than five days.
With both datasets in hand, "now I think you can look differently at that Gilead data," Wolfe said. "Not only ought we be using remdesivir, but we can think carefully about how long we use it for."
Although Gilead said remdesivir was well tolerated in its study, 3% of patients discontinued treatment due to signs of liver toxicity and 7% of those treated overall stopped taking remdesivir.
The NIAID study results will intensify the spotlight on Gilead, which has been under pressure to provide access to remdesivir through compassionate use.
In April, the drugmaker said it would donate its current supply of the drug — some 1.5 million individual doses — for use in patient access programs and for initial distribution following a regulatory authorization. Initially, Gilead estimated that would be enough for 140,000 treatment courses lasting 10 days. If only 5 days of treatment are needed, those 1.5 million doses could in theory cover twice as many patients.
The company is quickly ramping up production and aims to make enough drug for 800,000 drug courses by October, and more than 1 million by the end of the year.
Gilead could quickly face rising demand for its drug, too, as the results could shift what's considered standard of care in treating COVID-19.
The NIAID trial, for example, was designed to be adaptive, testing multiple promising therapies in succession. With supporting data now in hand, remdesivir will be used as part of the control arm in the study's next test, comparing remdesivir plus an arthritis drug called Olumiant against remdesivir and placebo, UVA's Bell said.
Data from another trial run by Gilead, in moderate patients, are expected by the end of May and could further clarify remdesivir's effectiveness.