Gilead Sciences' antiviral drug remdesivir had "little or no effect on mortality" among hospitalized patients with Covid-19, according to interim data released Thursday in a preprint study by scientists from the World Health Organization (WHO).
US new coronavirus cases top 8M, deaths surpass 217K
The findings come as U.S. officials as of Friday morning reported a total of 8,020,100 cases of the novel coronavirus since the country's epidemic began—up from about 7,954,700 cases reported as of Thursday morning.
According to the New York Times, the United States' average daily number of newly reported coronavirus cases over the past week was 54,399—which is up by 25% when compared with the average from two weeks ago. The country reported 65,327 new cases of the virus on Thursday, the Times reports.
Data from the Times shows that the rates of newly reported coronavirus cases are "staying high" in Guam and 28 states that have had a daily average of at least 15 newly reported cases per 100,000 people over the past week. Those states are Alabama, Alaska, Arkansas, Colorado, Idaho, Illinois, Indiana, Iowa, Kansas, Kentucky, Minnesota, Mississippi, Missouri, Montana, Nebraska, Nevada, New Mexico, North Carolina, North Dakota, Oklahoma, Rhode Island, South Carolina, South Dakota, Tennessee, Texas, Utah, Wisconsin, and Wyoming.
Meanwhile, the rate of newly reported cases over the past seven days is "going down" in Puerto Rico, which had previously seen elevated case rates.
Washington, D.C., and 15 states that have had comparatively low case rates are now seeing those rates "going up," according to the Times. Those states are Arizona, Connecticut, Florida, Massachusetts, Michigan, New Hampshire, New Jersey, New York, Ohio, Oregon, Pennsylvania, Vermont, Virginia, Washington, and West Virginia.
In the eight remaining U.S. states and territories, rates of newly reported coronavirus cases are "staying low," according to the Times' analysis.
The United States also reported at least 793 new deaths linked to the coronavirus on Thursday, the Times reports. U.S. officials as of Friday morning reported a total of 217,585 deaths linked to the coronavirus since the country's epidemic began—up from about 216,792 deaths reported as of Thursday morning.
WHO study shows remdesivir and three other drugs did not improve survival among Covid-19 patients
As the numbers of novel coronavirus cases and related deaths continue to rise in the United States and around the world, researchers have been scrambling to discover a treatment for Covid-19, the disease caused by the virus. Gilead's remdesivir quickly emerged as one of the most promising experimental treatments for Covid-19, and FDA earlier this year issued an emergency use authorization (EUA) allowing providers to use the drug to treat patients with severe cases of the disease. Later, FDA expanded remdesivir's EUA to include all hospitalized Covid-19 patients, regardless of the severity of their illness.
In May, preliminary data published from a clinical trial led by the National Institute of Allergy and Infectious Diseases showed that remdesivir was associated with faster recovery times among some patients. Final data from the trial released last week similarly showed remdesivir quickened recovery times among certain Covid-19 patients—and a post-hoc analysis of the data suggested that remdesivir decreased the risk of death among Covid-19 patients who required oxygen. In addition, an analysis released by Gilead in July showed that Covid-19 patients treated with remdesivir recovered sooner and were 62% less likely to die when compared with data from a historical control group.
However, on Thursday, interim data from a clinical trial sponsored by WHO showed remdesivir did not prevent deaths among Covid-19 patients. The data, which has not yet been peer-reviewed, was published early in medRxiv while it awaits publication in the New England Journal of Medicine.
WHO's Solidarity Therapeutics trial—which enrolled more than 11,300 adults with Covid-19 in 405 hospitals across 30 countries—evaluated four drugs: hydroxychloroquine, interferon, remdesivir, and an HIV antiviral that combines lopinavir and ritonavir. "The protocol was designed to involve hundreds of potentially over-stressed hospitals in dozens of countries," the researchers wrote in the study.
Ultimately, the researchers found that, when compared with the control groups, none of the treatments reduced mortality among Covid-19 patients, the likelihood a patient would need mechanical ventilation, or the time spent in the hospital. "For each drug in the study, the effect on mortality was disappointingly unpromising," WHO said in a statement.
According to Science Magazine, the prospects of two of the four treatments studied—hydroxychloroquine and the HIV drug combination—had "faded" after a study in June demonstrated that neither treatment increased survival. WHO dropped both of those treatments from its trial after assessing the findings of that larger study and its own data that had been collected up until that time, Science Magazine reports.
Meanwhile, for remdesivir specifically, the researchers found that of the 2,743 hospitalized Covid-19 patients who received the drug, 11% died, compared with 11.2% among a control group—a difference so minor that it could result from chance, according to the study. Moreover, when the researchers pooled their data on the drug with data from three other trials on remdesivir, the mortality risk was reduced so slightly that it wasn't considered statistically significant. "This absolutely excludes the suggestion that remdesivir can prevent a substantial fraction of all deaths," the researchers wrote.
And concerning interferon-beta, the researchers found that of the 2,050 people who received the drug, 11.9% died, compared with 10.5% in the control group.
The researchers said the Solidarity trial would continue, aiming to continue collecting evidence on remdesivir and adding new drugs to assess, including newer antivirals, "immunomodulators, and … monoclonal antibodies" to the novel coronavirus.
What do the new findings mean?
Ilan Schwartz, an infectious-disease physician at the University of Alberta, said the new data "puts the issue to rest—there is certainly no mortality benefit."
However, Peter Chin-Hong, an infectious-disease expert at the University of California-San Francisco, said there may have been inconsistent treatment protocols across the health systems involved in the trial, which may have affected the results. "So much goes into care," Chin-Hong said. "The drug is only part of it."
Similarly, Gilead in a statement pushed back on the results, saying, "The emerging data appear[s] inconsistent with more robust evidence from multiple randomized, controlled studies published in peer-reviewed journals validating the clinical benefit of [remdesivir]. We are concerned that the data from this open-label global trial have not undergone the rigorous review required to allow for constructive scientific discussion."
Gilead added, "The benefits of [remdesivir] have been demonstrated in three randomized, controlled clinical trials, including a randomized, double-blind, placebo-controlled clinical trial—the gold standard for evaluating the efficacy and safety of investigational drugs."
Schwartz and Maricar Malinis, an infectious disease physician at Yale University, agreed that remdesivir may help Covid-19 patients, but they noted that patients may only benefit from the drug when they receive it early during their illness—before their body's immune system goes into overdrive. When patients receive the drug too late, "the horse is [already] out of the barn," Schwartz said.
Separately, Eric Topol, director of the Scripps Research Translational Institute, said while the findings on interferon-beta were the study's "most disappointing" results, earlier studies have indicated that the treatment is only beneficial when given earlier in the course of illness—not after patients require hospitalization. "So I think that's still an open question," Topol said (Bonifield, CNN, 10/16; Wu/Kolata, New York Times, 10/15; Kupferschmidt, Science Magazine, 10/16; New York Times, 10/16).