- Treatment with Gilead's antiviral drug Veklury did not prevent deaths among patients hospitalized with COVID-19, results from a large, international trial run by the World Health Organization showed, suggesting the drug's benefit is more limited than previous studies have indicated.
- Veklury, also known as remdesivir, is approved or otherwise authorized for use in roughly 50 countries, largely due to positive data from a National Institutes of Health trial in the U.S. that indicated treatment shortened patients' time to recovery.
- The NIH study didn't definitively prove Veklury prevented COVID-19 deaths, but suggested a possible benefit among certain, less-sick patients. That conclusion is now much more in doubt in light of the WHO study results, which were published online Thursday and have not yet been peer reviewed.
Veklury, originally developed by Gilead for use in hepatitis C and then Ebola virus infections, is the only antiviral drug authorized in the U.S. to treat COVID-19.
While the benefit shown in the NIH's key study was modest, Veklury has become standard treatment for patients hospitalized with COVID-19 before they get so sick as to require intensive care. Tens of thousands of U.S. patients have received the drug, including President Donald Trump, whose physicians included Veklury in an aggressive course of several experimental medicines.
As a sign of its rapid incorporation into COVID-19 treatment, clinical studies testing newer drugs developed specifically for coronavirus disease now include Veklury as part of baseline care.
But no randomized, placebo-controlled study has proven Veklury can actually prevent deaths from COVID-19. In the NIH study, known as ACTT-1, treatment with Veklury shortened the time to clinical recovery by four days compared to placebo. After 28 days, fewer deaths had occurred among Veklury-treated patients than those given placebo, but the difference was not large enough to conclusively say the drug was the reason why.
The WHO's larger trial, which tested Veklury and three other repurposed medicines, returned a much different result, concluding all four treatments had "little or no effect" on reducing the risk of death, use of mechanical ventilation or time to recovery.
"The unpromising overall findings from the regimens tested suffice to refute early hopes, based on smaller or non-randomized studies, that any will substantially reduce inpatient mortality, initiation of ventilation or hospitalization duration," researchers in the trial, called SOLIDARITY, wrote.
Their findings were made public in a pre-print manuscript, and haven't gone through the rigorous process of peer-review. And while the study randomized participants between treatment and control groups, there was no placebo given, meaning doctors knew whether they were giving an experimental medicine. While that may not bias outcomes like death, the open-label nature of the study could in theory influence more malleable measures like time to recovery.
Still, the large size of the trial — more than 11,000 patients received one of the four drugs on top of supportive care, or supportive care alone — and the imprimatur of the WHO give the data added weight. Indeed, the data from SOLIDARITY represent three-quarters of the clinical evidence from randomized clinical trials for remdesivir, the researchers noted.
Squaring the WHO trial results with the NIH trial results is difficult, according to Taison Bell, an assistant professor of medicine and infectious disease doctor at the University of Virginia. But he said the SOLIDARITY results do not rule out a role for Veklury, when given at the right time to the right patients.
The SOLIDARITY manuscript, for example, presented results for patients on low- and high-flow oxygen together, whereas ACTT-1 separated data from those two groups and found a much larger benefit for those on low-flow oxygen support.
"It's an important clinical difference," Bell said in an interview, noting those on high-flow oxygen are critically ill and more likely to be transferred to intensive care, where remdesivir isn't thought to be helpful.
Still, Bell added, "if remdesivir was the silver bullet, we would see positive effects across different times of administration and disease severity. But it's not that kind of drug." Bell was involved with conducting ACTT-1.
In a statement, Gilead sharply disputed the WHO trial's findings and criticized the study's design as allowing for "significant heterogeneity" in how the trial was enrolled and implemented.
"[C]onsequently, it is unclear if any conclusive findings can be drawn from the study results," the company said.
Gilead is currently asking the FDA for full approval of Veklury — rather than only an emergency use authorization — and has staked a lot on the drug financially, investing hundreds of millions of dollars into its development and betting on its potential to earn much more.
"Although the FDA probably doesn't have it in them to pull an EUA, this could jeopardize full approval, which is currently under review," wrote analysts at R.W. Baird in an Oct. 15 note to clients. "We believe it will certainly see a limitation of use, especially outside the U.S."
Gilead recently took over responsibility for distributing the drug in the U.S., a role that had been temporarily handled by the U.S. government while supplies were limited.
The drug's price, set by Gilead between $2,340 and $3,120 for the typical five-day course, could also be called into question. The Institute for Clinical and Economic Review, a powerful drug pricing watchdog, largely supported Gilead's pricing, but noted that without a mortality benefit, the drug would only be cost-effective at a price of about $310 per course.
Editor's note: This article has been updated to mention the involvement of Taison Bell in the ACTT-1 study.