The government’s first rigorous clinical trial of the experimental drug remdesivir as a coronavirus treatment delivered mixed results to the medical community Wednesday — but rallied stock markets and raised hopes that an early weapon to help some patients was at hand.
The preliminary results, disclosed at the White House by Anthony Fauci, chief of the National Institute of Allergy and Infectious Diseases, which led the placebo-controlled trial, found that the drug accelerated the recovery of hospitalized patients but had only a marginal benefit in the rate of death.
That falls short of the magic bullet or cure that many were hoping for in Gilead’s drug. But with no approved treatments for COVID-19, Fauci said, it will become the standard of care for hospitalized patients and serve as a key building block as clinicians hone their approach.
The drug accelerated the recovery time of infected patients by 31%, from 15 days in patients who got a placebo to 11 days in people treated with remdesivir, Fauci said. But it only reduced the death rate from 11% to 8%, which Fauci said lacked statistical significance.
“The data shows that remdesivir has a clear-cut, significant, positive effect in diminishing the time to recovery,” Fauci said. “Although a 31 percent improvement doesn’t seem like a knockout 100 percent, it is a very important proof of concept.” He said it shows that the virus is vulnerable to drug treatments that use the remdesivir approach, which is to block enzymes that allow the virus to replicate.
Fauci’s remarks boosted speculation that the Food and Drug Administration would seek emergency use authorization that would permit doctors to prescribe the drug.
In addition to clinical trials, remdesivir has been given to more than 1,000 patients under compassionate use.
The study, involving 1,000 patients at 68 sites in the United States and around the world, offers the first evidence from a large, randomized clinical study of remdesivir’s effectiveness against COVID-19.
The trial was launched in February in record time, with the first patient recruited from infected passengers evacuated from the cruise ship Diamond Princess on Feb. 17. That patient went to the University of Nebraska, which is home to the National Quarantine Center.
The drug must be given intravenously over 5 to 10 days and the NIAID trial results only apply to hospitalized patients. Remdesivir is not intended for use in the majority of patients, estimated to be 80% or more, who are infected with coronavirus but do not require hospitalization.
Eric Topol, director of the Scripps Research Translational Institute in La Jolla, California, said that remdesivir “isn’t a breakthrough drug,” and that the totality of evidence, with its mix of good and bad results, offers a “confusing picture.” But he said the drug is a “good start. It has efficacy and it’s safe.”
A number of leaked trial results and small remdesivir studies without placebo controls have whipsawed stock markets in recent weeks, highlighting the intense desire among investors and political leaders for a therapy that can beat back the virus.
Speeding recoveries and reducing the length of hospital stays can ease the burden on the health system and give business and political leaders greater confidence as they seek to relax social distancing and economic lockdowns across the country.
The results from the NIAID study were not published in a medical journal, but Fauci said that step will be made soon. Once they are, clinicians can pore over the data in detail to see which patients will benefit the most.
Fauci said the drug will now be tested in combination with anti-inflammatory drugs in an NIH-sponsored trial. He likened the advance on Wednesday to the use of AZT in the mid-1980s to treat AIDS, the disease caused by HIV. Remdesivir likely will serve as a basis for drug cocktails and better antivirals, experts said.
“You have to get your foot in the door, and this is a good first step for sure,” Rajesh Gandhi, an infectious disease doctor at Massachusetts General Hospital and Harvard Medical School professor who helps develop treatment guidelines for the Infectious Diseases Society of America. “We’re all excited because those top line results look favorable. There is more to come, and that will help us understand a lot more than we do today.”
Fauci said he received a report from the trial’s leaders on Monday. He said he announced preliminary results early, before they were published, out of ethical concerns, so that patients receiving a placebo can opt to get the drug instead.
“In general this is an encouraging result,” said Amesh Adalja, a senior scholar at the Johns Hopkins University Center for Health Security. “People were very hopeful for remdesivir. The next step is going to be really important to fine tune our use of it and use it on the patients who will benefit maximally from it.
“There’s clearly going to be people who don’t need it, who are going to get better on their own, and there’s going to be people who are too sick to get it,” he said.
The announcement is expected to boost demand significantly, potentially leading to shortages. Gilead has said it is ramping up production capacity in anticipation of approval and to meet demand in clinical trials and through compassionate use, which allows doctors to apply for the drug for individual patients.
The company has said it expects to have 1.5 million doses available by the end of May, which could satisfy demand for more than 140,000 patients.
The stock market shot up nearly 2% early after Gilead Sciences announced Wednesday morning that NIAID would be releasing positive early results.
“Certainly it’s a, it’s a positive, it’s a very positive event,” Trump said in response to Fauci’s remarks, according to a White House press pool report.
Remdesivir was invented by Gilead a decade ago and has shown promise against a variety of viruses in laboratory and animal experiments. But in its first trial in humans, in Ebola cases in Africa in 2019, it did not show benefit when compared to other drugs in the same study.
The NIAID study is the most rigorous test to date of the potential treatment because it is a double-blind, placebo-controlled trial, the gold standard for seeing if a drug is safe and effective. A cohort of patients receive a dummy treatment instead of the real drug, without patients and treating doctors knowing which one the patients are getting. It provides the best comparison of how people treated with the drug fared in relation to those who did not get the drug.
“As part of the FDA’s commitment to expediting the development and availability of potential COVID-19 treatments, the agency has been engaged in sustained and ongoing discussions with Gilead Sciences regarding making remdesivir available to patients as quickly as possible, as appropriate,” FDA spokesman Michael Felberbaum said.
Remdesivir can have serious side effects, according to previous trial results, including loss of kidney function and declining blood pressure. Those symptoms are caused by severe cases of coronavirus, as well, making it difficult to determine which problems were caused by the drug and which by the illness.
In a separate statement, Gilead released some results of its own clinical trial that showed a five-day course of treatment of remdesivir produced similar results to 10 days of treatment.
The finding is a sign that, if approved, more people could receive limited supplies of the drug and that patients could spend less time in the hospital. Gilead said it plans to submit the full data for publication in a peer-reviewed journal in the coming weeks.
“The study demonstrates the potential for some patients to be treated with a 5-day regimen, which could significantly expand the number of patients who could be treated with our current supply of remdesivir,” Merdad Parsey, Gilead’s chief medical officer, said in a news release. “This is particularly important in the setting of a pandemic, to help hospitals and health care workers treat more patients in urgent need of care. “
Gilead also said that people who were given the drug within 10 days of first showing symptoms fared somewhat better than patients who were given the drug later. “By Day 14, 62% of patients treated early were able to be discharged from the hospital, compared with 49% of patients who were treated late,” the company said.
The medical journal The Lancet Wednesday released results of a negative clinical trial of remdesivir in China that was terminated early because investigators, as the China outbreak subsided, were unable to recruit all of the 453 patients they sought. In the 237 patients that did participate in the placebo-controlled trial, there was no statistically significant difference in time to clinical improvement, the Chinese investigators reported. Deaths were roughly the same, with 14%, (22/158) patients dying in the remdesivir group, compared with 13% (10/78) in the placebo group.