Three dozen patients with COVID-19 given an experimental Gilead drug called remdesivir appeared to improve in the days following treatment, raising some hope the antiviral therapy could prove beneficial in larger and more rigorous studies that are currently ongoing.
The results are not from a clinical trial, but rather amassed from 53 people who received the drug through compassionate use programs designed to allow patients with few options early access to medicines still in development.
There was no control group to compare against, and investigators didn't collect data showing how much virus was in patients' bodies before or after treatment with remdesivir. That makes it impossible to conclude whether the improvements observed in 36 patients were due to Gilead's drug. Seven people in the group died, while the condition of 10 remained the same.
Details of how the patients fared were published Friday in the New England Journal of Medicine, setting the stage for later this month, when Gilead expects the first data from a randomized trial of the drug. Seven clinical studies are ongoing, including two being run by Gilead and another by the National Institutes of Health.
"In the broader efforts to determine whether it is a safe and effective treatment, we have some way to go," wrote Gilead CEO Daniel O'Day in an open letter addressing the published results.
Randomized studies of Gilead's remdesivir in COVID-19
|Study sponsor||Patient population, target n||Status|
|Gilead||Severe disease, 2400||Enrolling, data due in April|
|Gilead||Moderate disease, 1600||Enrolling, data due in May|
|NIAID||Hospitalized adults, 440||Enrolling, data due in May|
|Capital Medical Univ. (China)||Severe disease, N/A||Terminated early due to low enrollment|
|Capital Medical Univ. (China)||Mild to moderate disease, 308||Enrolling|
|World Health Organization||Hospitalized adults, N/A||Enrolling, data after June|
|INSERM||Hospitalized adults, 3100||Enrolling, data after June|
SOURCE: Company, clinicaltrials.gov
Remdesivir is one of many antiviral therapies being tested in COVID-19, but many see it as promising. Originally developed for the Ebola virus, the drug works by preventing viruses like SARS-CoV-2 from using the body's cells to reproduce themselves. Preclinical experiments in human cell cultures and mice indicated remdesivir could be active against the new coronavirus, although similar signs suggested it could work against Ebola only for it to fall short in clinical testing.
Since January, when infections began to quickly mount in China and spread elsewhere, Gilead has provided remdesivir to COVID-19 patients via compassionate use. Some 1,800 people have been treated this way globally. The biotech recently switched to supplying the drug through broader expanded access programs, with some exceptions.
The 53 patients included in the NEJM publication were among the first to receive remdesivir, having taken at least one dose of the drug by March 7. The patients included reflect the coronavirus' transmission across the globe. Twenty-three were from the U.S. and Canada, nine were from Japan and 21 were from six countries in Western Europe.
Two-thirds of the group were on invasive mechanical ventilation or advanced respiratory support when requests for compassionate use access to remdesivir were granted. Seventeen were taken off ventilation following treatment, a signal of potential effectiveness that study authors described as notable.
"We cannot draw definitive conclusions from these data, but the observations from this group of hospitalized patients who received remdesivir are hopeful," said Jonathan Grein, a director of epidemiology at Cedars-Sinai Medical Center in Los Angeles and the lead author of the study, in a statement provided by Gilead.
Overall, 36 of the 53 patients improved sufficiently to be moved to less intensive respiratory support, defined by a six-point scale. Twenty-five, mostly those who were breathing ambient air or via low-flow oxygen at baseline, were discharged from the hospital.
Without a control group to compare those results to, however, it's not clear whether remdesivir drove patients' recovery. And while the 13% death rate recorded for the group would compare favorably to what's been seen in other studies and case series, patients were followed for a median of only 18 days. Twenty-one patients were still in the hospital and at risk of dying when data collection stopped, which could make the numbers as of study cut-off appear more favorable.
Eight patients were also excluded from the start, due to missing post-baseline information.
More positively, however, investigators didn't find signs of any unexpected side effects from the drug. Because remdesivir was rushed into clinical testing for COVID-19, less is known about its potential harms in a severe patient population that tends to be older and to often have other health problems like high blood pressure and diabetes.
The published data aren't meant to answer many of the questions that can only be addressed by a randomized study. Yet, with coronavirus case counts and deaths rising rapidly in many countries, the results could ratchet up pressure on Gilead to make the drug available more widely sooner. More than 490,000 people in the U.S. have been confirmed to be infected through April 11, according to data from the Centers for Disease Control and Prevention, and nearly 19,000 people have died.
In the U.S., President Donald Trump has seized upon shreds of early evidence for the anti-malaria drug hydroxychloroquine to push for its use before studies can prove it works to curb COVID-19 symptoms. In late March, the Food and Drug Administration granted an emergency authorization to two versions of the pill, allowing distribution of millions of doses from federal stockpiles to states and hospitals.
Fortunately, Gilead expects to report within weeks data from the first of its two Phase 3 studies of remdesivir, which are being conducted in the U.S. and certain Asian countries. Results could also come soon from two trials in China, although less is known about how those have progressed. One, in patients with severe COVID-19, was stopped early due to low enrollment, Gilead confirmed Friday.
Even if remdesivir does prove effective in those trials, the benefit may not be as large as some expect. Antiviral drugs usually work better when given early on, and don't always offer dramatic improvements in symptoms — something even Gilead has acknowledged.
"Even when you have the opportunity to design molecules for specific pathogens, it's hard to be successful. And the timing of drug use can matter a lot," said Merdad Parsey, Gilead's chief medical officer, in an interview with C&EN published April 10.
"So there can be and probably will be a mismatch between what we're going to be able to demonstrate and what the public's expectations are."