Patients are recovering from COVID-19 when they are given the experimental drug remdesivir, according to two separate studies by the Peninsula company that makes the drug and the National Institute of Allergy and Infectious Diseases announced on Wednesday, April 29. The Food and Drug Administration approved its use on an emergency basis on Friday, May 1.
Preliminary data from NIAID's study shows the antiviral drug, developed by Foster City-based Gilead Sciences Inc., helped hospitalized patients with advanced COVID-19 affecting their lungs recover faster than similar patients who received a placebo. The randomized, controlled study involved 1,063 patients, the institute said.
NIAID's Adaptive COVID-19 Treatment Trial, which began on Feb. 21, found that remdesivir was better than a placebo from the time of recovery, which is a metric often used in influenza trials. Recovery in the study was defined as being well enough for hospital discharge or returning to normal activity.
Patients who received remdesivir had a 31% faster recovery time than those who received the placebo. Patients treated with remdesivir had a median recovery time of 11 days compared to 15 days for those who received the placebo. Results also suggested a lower death rate among those who received the drug, with a mortality rate of 8% for the group receiving remdesivir versus 11.6% for the placebo group, NIAID said.
The first participant was an American who was repatriated after being quarantined on a Diamond Princess cruise ship that docked in Yokohama, Japan. The patient volunteered to participate in the trial at the first study site, the University of Nebraska Medical Center/Nebraska Medicine, in February. A total of 68 sites ultimately joined the study — 47 in the United States and 21 in countries in Europe and Asia, NIAID said.
More detailed information about the trial results, including more comprehensive data, will be available in a forthcoming report. NIAID also will provide an update on the plans for the trial at a later date.
NIAID Director Dr. Anthony Fauci said during a press conference on Wednesday, April 29, that the diminished death rate from the treatment has not yet reached statistical significance, but the data needs to be further analyzed. An independent data and safety board monitoring the study notified him last Friday and again on Monday that the trial data showed a "clear-cut, positive effect in diminishing time to recover," he said. "It's highly significant," he said.
"Although a 31% improvement doesn't seem like a knock-out 100%, it is a very important proof of concept, because what it has proven is a drug can block this virus," he said.
"All of the other trials that are taking place now have a new standard of care," he added.
Fauci said the remdesivir trial is reminiscent of research conducted 34 years ago when he and others were looking at the human immunodeficiency virus (HIV). At the time, there were no treatments. They performed the first drug tests with the antiretroviral drug azidothymidine (AZT), which had a modest effect on HIV and were able to build on it to create more effective drugs, he said. Fauci thinks the same will be true with remdesivir.
Researchers will now compare a combination of remdesivir with an anti-inflammatory drug, a monoclonal antibody, he said.
Gilead also announced the results of the first of its two clinical trials in a separate statement Wednesday. The company initiated two randomized Phase 3 clinical trials for remdesivir, the Simple studies, in countries with a high prevalence of COVID-19 infection.
In Gilead's first trial, researchers gave five-day and 10-day doses of remdesivir intravenously to 397 hospitalized patients who had severe cases of the disease. Both treatments had similar results and neither study group showed any new safety concerns from the medication, the company said.
Gilead said it plans to submit the full data for publication in a peer-reviewed journal in coming weeks.
"Unlike traditional drug development, we are attempting to evaluate an investigational agent alongside an evolving global pandemic. Multiple concurrent studies are helping inform whether remdesivir is a safe and effective treatment for COVID-19 and how to best utilize the drug," Dr. Merdad Parsey, Gilead Sciences' chief medical officer, said in the company statement.
"These study results complement data from a placebo-controlled study of remdesivir conducted by the National Institute for Allergy and Infectious Diseases and help to determine the optimal duration of treatment with remdesivir. 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. 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."
Remdesivir isn't licensed or approved and has not yet been demonstrated to be safe or effective for the treatment of COVID-19, the statement noted. The study sought to determine whether a shorter, five-day course of remdesivir would be as effective as a 10-day treatment regimen used in multiple ongoing studies of the drug. It included rates of adverse events and other measures of clinical response in both treatment groups.
All of the patients had pneumonia and reduced oxygen levels, but they did not require mechanical ventilation when they entered the study. The patients achieved clinical recovery if they no longer required oxygen support and medical care or were discharged from the hospital.
Clinical improvement was defined as a positive change of two or more points from the patient's baseline on a seven-point scale, which ranged from hospital discharge to increasing levels of oxygen support.
Fifty percent of patients who received treatment showed improvement in 10 days among the five-day treatment group and 11 days in the 10-day treatment group. More than half of patients in both treatment groups were discharged from the hospital by day 14, with 64.5% of patients in the five-day treatment group and 53.8% of patients in the 10-day treatment group achieving clinical recovery.
Patients who were given remdesivir earlier also had improved outcomes. Participants who received the drug within 10 days of the onset of symptoms fared better than those treated more than 10 days into the disease. By day 14, 62% of patients who treated early in their illness were cleared for hospital discharge. Of patients who were treated later in their illness, only 49% were cleared to leave the hospital.
Remdesivir was generally well-tolerated in both the five-day and 10-day treatment groups, the company said. The most common adverse events that occurred in more than 10% of patients in either group were nausea and acute respiratory failure. Elevated liver enzymes occurred in 7.3% of patients, with 3% exiting the trial due to the increased liver enzymes.
An expansion phase of this study will enroll an additional 5,600 patients, including patients on mechanical ventilation. The study is being conducted at 180 trial sites around the world, including in the United States, China, France, Germany, Hong Kong, Italy, Japan, Korea, the Netherlands, Singapore, Spain, Sweden, Switzerland, Taiwan and the United Kingdom, the company said.
A second trial study is evaluating the safety and effectiveness of five-day and 10-day remdesivir dosing in patients with moderate COVID-19 symptoms compared with the standard of care. The results from the first 600 patients of this study are expected at the end of May.
Palo Alto resident Monica Yeung-Arima, who was one of the patients in Gilead's first remdesivir trial, said on Wednesday that she is gratified by the trial results. Yeung-Arima was given a five-day treatment with remdesivir starting March 13. She began to recover three days into her treatment.
"I am so glad that I'm one of the guinea pigs. I am getting better every day. I am thankful," Yeung-Arima said in a text message to this news organization.
"I'm so glad that there's positive news on remdesivir and the drug can possibly be used by many patients soon. It would be nice if the drug can treat more than one virus so it could do good for the near future. It also can put many people at ease to have a solution, even if it's not a 100% cure," she said.
On May 1, the Food and Drug Administration approved emergency use remdesivir.
"It is reasonable to believe that the known and potential benefits of (remdesivir) outweigh the known and potential risks of the drug for the treatment of patients hospitalized with severe COVID-19," the FDA wrote in its approval letter.
The drug will only be used on adults and children with suspected or laboratory confirmed cases of COVID-19 and severe disease, which was defined as a patient who has a blood oxygen level of 94% or less when breathing normal room air, requiring supplemental oxygen, mechanical ventilation or life support.
Gilead will supply the drug to authorized distributors or directly to a U.S. government agency, which will distribute remdesivir to hospitals and other health care facilities in collaboration with federal, state and local authorities.
Find comprehensive coverage on the Midpeninsula's response to the new coronavirus by Palo Alto Online, the Mountain View Voice and the Almanac here.