By Katherine J. Wu and Gina Kolata
Remdesivir, the only antiviral drug authorized for treatment of Covid-19 in the United States, fails to prevent deaths among patients, according to a study of more than 11,000 people in 30 countries sponsored by the World Health Organization.
The drug was granted emergency authorization by the Food and Drug Administration on May 1 after a trial by the National Institutes of Health found that remdesivir modestly reduced the time to recovery in hospitalized patients. President Trump received the antiviral after he began showing symptoms earlier this month.
“This puts the issue to rest — there is certainly no mortality benefit,” said Dr. Ilan Schwartz, an infectious disease physician at the University of Alberta in Canada.
But other scientists said the design of the W.H.O.’s sprawling clinical trial, which collected data from hundreds of hospitals, meant the conclusions were not definitive.
Conducted in dozens of countries with various health care systems and inconsistent treatment protocols, the data are difficult to analyze and compare, said Dr. Peter Chin-Hong, an infectious disease expert at the University of California, San Francisco.
The findings, which were posted online on Thursday, have not yet been peer-reviewed or published in a scientific journal.
Remdesivir, which was originally developed as a treatment for Ebola and hepatitis C, interferes with the reproduction of viruses by jamming itself into new viral genes.
The N.I.H. study also did not find that remdesivir prevented deaths in patients with Covid-19. Dr. Anthony Fauci, director of the National Institute of Allergy and Infectious Diseases, acknowledged in the spring that remdesivir was not a “knockout” drug.
A final analysis, published in The New England Journal of Medicine on Oct. 8, suggested “a trend toward reduced mortality” in certain patients receiving remdesivir, according to the drug’s maker, Gilead.
Gilead disputed the conclusions of the W.H.O. study on Thursday, noting that a variety of drugs and drug combinations had been evaluated under a wide range of circumstances and that more rigorous studies had found a benefit.
“Consequently, it is unclear if any conclusive findings can be drawn from the study results,” the company said in a prepared statement.
Dr. Andre Kalil, a principal investigator of the federal study of remdesivir and an infectious disease expert at the University of Nebraska Medical Center, faulted the W.H.O. trial for not having a placebo group, and for allowing patients and doctors to know which treatments were administered. So-called open-label trials can skew the reporting of results.
There was “a large amount of missing data” on the patients, he added, which “cannot be fixed by a large sample size, no matter how large it is.”
The antiviral has been administered to thousands of patients since its emergency authorization. The drug costs $3,120 per treatment course for patients with private insurance in the United States.
Although originally cleared only for use in people who were sick enough to need supplemental oxygen or breathing support, remdesivir’s emergency authorization was expanded in August to include all hospitalized patients, regardless of disease severity.
The move was criticized by some experts, who said the F.D.A. had made the shift without sufficient evidence.
The W.H.O.’s study, called the Solidarity trial, enrolled more than 11,300 adults with Covid-19 in 405 hospitals in 30 countries. The participants were given four drugs singly or in combination: remdesivir, hydroxychloroquine, lopinavir, interferon or interferon plus lopinavir. About 4,100 received no drug treatment.
In the end, no drug or combination reduced mortality, the chances that mechanical ventilation would be needed, or time spent in the hospital, compared with the patients without drug treatment.
Several previous studies had pointed to the futility of hydroxychloroquine and lopinavir as treatments against the coronavirus. Less data has been published on interferon, a molecule produced by the immune system in response to viruses.
In their manuscript, the study’s authors called the overall findings “unpromising” and said they “suffice to refute early hopes” that any of the drugs tested “will substantially reduce inpatient mortality, initiation of ventilation or hospitalization duration.”
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The remdesivir findings aren’t terribly surprising, based on previous research, but they are “still impactful,” especially given the dizzying size of the Solidarity trial, said Dr. Maricar Malinis, an infectious disease specialist at Yale University.
Still, several experts noted that some of the drugs in the trial may benefit people with Covid-19 earlier in the course of their illness.
“All the emerging evidence points to interferon treatment being effective at the early, viral phase of Covid-19,” said Eleanor Fish, an immunologist at the University of Toronto.
Until enough data emerge to group patients by factors like the stage of disease they are in, “it is premature to dismiss some of these repurposed drugs as ‘ineffective’ and to suggest they should not be evaluated further,” Dr. Fish said.
As for remdesivir, “I don’t think this study is the nail in the coffin,” said Dr. Taison Bell, a critical care physician at the University of Virginia. “But I do think it shows that we have to be selective about the patient population we use it in.”
Mr. Trump, who was hospitalized on Oct. 2, the day after his diagnosis, may have been well-suited to receive remdesivir, Dr. Bell said.
The president had not been symptomatic for long, and though his oxygen levels dropped on two occasions, his doctors did not need to put the president on a breathing machine. He did receive supplemental oxygen.
Severe Covid-19 is thought to be driven largely by an overly exuberant immune response that starts several days after the virus infects the body. Before that happens, an antiviral might tamp down the virus enough to protect a person from the immune system’s overreaction.
Administering remdesivir after that stage may be pointless, Dr. Schwartz said, adding, “The horse is out of the barn.”