A candidate treatment for COVID-19 has shown convincing—albeit modest—benefit for the first time in a large, carefully controlled clinical trial in hospitalized patients.
The infected people who received remdesivir, an experimental drug made by Gilead Sciences that cripples an enzyme several viruses use to copy their RNA, recovered in an average of 11 days versus 15 in patients who received a placebo. “Although a 31% improvement doesn’t seem like a knockout, 100% [success], it is a very important proof of concept,” said Anthony Fauci, head of the National Institute of Allergy and Infectious Diseases (NIAID), during an Oval Office meeting in which President Donald Trump was asked by media about a statement Gilead had released on the results. The patients treated with remdesivir also had a lower mortality rate—8% versus 11.6% in the group given the placebo—but this positive trend did not reach statistical significance, Fauci noted. (The full results from the trial have not been made public in a preprint or peer-reviewed paper.)
NIAID sponsored the study, which began on 21 February and enrolled 1063 patients at 68 sites in the United States, Europe, and Asia. A board that monitors safety and data from the trial informed investigators on 27 April that remdesivir was better than the placebo. Fauci says the board is releasing the overall results early in part on ethical grounds: Given the positive data, remdesivir must now be offered to all study participants, and trials of other treatments now underway must start to offer the drug instead of a placebo, Fauci said.
The search for COVID-19 treatments that can do better than remdesivir remains a top priority. “It’s a promising signal, but we do not need to get hyperexcited—this is not a home run,” says Carlos del Rio, an infectious disease clinician at Emory University, one of the larger sites that participated in the remdesivir trial. In essence, he says, the study showed that patients who received the drug, which is given intravenously, could stop receiving supplemental oxygen earlier. Del Rio, a veteran of HIV drug development, which gradually advanced from nothing to effective treatments, hopes the results mark a first step for COVID-19. But he does not expect remdesivir will significantly ease the demands that COVID-19 is putting on hospitals, or brighten prospects for lifting shelter-in-place orders.
Nahid Bhadelia, who directs the special pathogens unit at Boston University School of Medicine and was not involved with the study, says she suspects remdesivir will have the most impact earlier in the course of disease. “It will be important to see from NIAID data whether that mortality benefit is greater for those with fewer than 10 days of symptoms,” Bhadelia says. “But you don’t want to start too early because the drug has side effects.” NIAID and Gilead have not yet reported on any adverse events experienced by patients in the trial, but other studies have linked remdesivir to blood abnormalities such as anemia.
Other studies of remdesivir have produced mixed results, with some showing no benefits and others generating positive outcomes. But each, by design or default, did not have the power of the NIAID-sponsored trial. One study with a placebo-control group appeared today in The Lancet and found no benefit of the treatment in 158 patients. Done in China, the trial was halted early because the country’s success in controlling viral spread meant there were not enough new patients to properly evaluate the drug. That study also found that remdesivir had no impact on viral levels, and it remains to be seen whether the NIAID-sponsored trial can connect the drug’s success to direct effects on the virus.
Frederick Hayden, a clinical virologist at the University of Virginia who co-authored The Lancet study, finds the evidence of benefit in the NIAID trial persuasive. Hayden notes that the Chinese researchers who led the trial reported in The Lancet did find that the subset of patients given remdesivir earlier in the disease course had faster times to clinical improvement and higher survival rates than those who received placebo, but these weren’t statistically significant findings. “There are parallels that are encouraging,” Hayden says.
Michael Saag, an infectious disease specialist at the University of Alabama, Birmingham, who cares for COVID-19 patients and had the disease himself for nearly 1 month, is much heartened by the positive new data. “Having ongoing viral replication is not a good thing, and I would like to shut it down and give the immune system the upper hand in clearing the infection,” says Saag, who treats people infected with HIV and hepatitis C virus. (Saag couldn’t obtain the remdesivir for himself because he wasn’t sick enough to qualify for studies or compassionate use.) “If remdesivir can work in people with advanced disease, even if it’s not dramatic, that gives me hope that the drug could be used earlier in the course of infection and have even better results, and that’s what we need to prove next.”
James Lawler, an infectious disease specialist at one of the sites in the NIAID-sponsored trial, the University of Nebraska Medical Center, says “it’s quite possible” remdesivir will receive approval from the U.S. Food and Drug Administration (FDA) for what’s known as emergency use. “Certainly, having a drug that has some proven efficacy will be helpful,” Lawler says. But he expects FDA would strictly limit which patients can get the drug, both because of supply issues and outstanding questions about its impact at different disease stages. “Given the scarcity, which is still going to be an issue, it’s not going to be readily available for everyone, and given the population in which it was studied and showed benefit, it’s most prudent to use it in people who are more severely ill or at least have higher risk factors and are in the hospital,” Lawler says.
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