What You Need to Know About Remdesivir, the Potential Coronavirus Drug
Doctors say it’s too soon for enthusiasm, and patients’ families are frustrated by the distribution of the drug
There’s promising first data on the effectiveness of the experimental drug remdesivir to treat Covid-19. Published Friday, April 10 in the New England Journal of Medicine, 36 out of 53 patients (68%) who received the drug showed signs of improvement, 25 of whom were eventually sent home. Seven people (13%) died. Of the 30 people who were on ventilators in the study, 57% were able to come off oxygen support.
For comparison, studies from China and the U.K. report that 86% and 66%, respectively, of Covid-19 patients who didn’t receive remdesivir died after being put on a ventilator.
Physicians involved in the remdesivir research say they are encouraged by the results, but they caution that the findings are preliminary. Most glaring, the data were not part of a clinical trial but come from compassionate use of the drug, which means there was no placebo arm to compare people who received it with those who did not. As a result, it is impossible to know whether the patients would have recovered at a similar rate without the medication. Several clinical trials are currently ongoing to provide this data.
“What we showed is there was some benefit, but we can’t really quantify it,” says Gary Green, MD, an infectious disease specialist at Sutter Santa Rosa Medical Hospital who treated two patients included in the analysis. “It was effective in vitro, and now we know it’s effective in vivo, but we can’t say how effective because we need to study it in a more tightly controlled manner.”
Other physicians who weren’t involved in the research aren’t as impressed with the findings and say the publication is premature. “These results are uninterpretable in the absence of a comparative control arm,” says Ilan Schwartz, MD, PhD, an assistant professor of medicine at the University of Alberta in the division of infectious diseases. “We have no way of knowing whether the outcomes reported in this study, good or bad, have anything to do with the drug.”
Infectious disease physician Krutika Kuppalli, MD, tweeted that the article was “exciting” and that remdesivir was a drug she “had my eye on from the start.” However, in an interview with Elemental she says that more information is needed, including details about the safety of the drug and long-term follow-up of the patients who received it. “I think this data is important in the sense that it gives us some information on patients who received the drug, but other than that you can’t really deduce anything,” says Kuppalli, who is a fellow at the Johns Hopkins University Center for Health Security. “I think it’s very hard in this setting to make any definitive claims about what this information means.”
“What we showed is there was some benefit, but we can’t really quantify it.”
Remdesivir is an experimental antiviral drug originally developed by the pharmaceutical company Gilead to treat Ebola. Although the medication proved to be relatively ineffective against Ebola, subsequent research in human cells and in animal models showed that it successfully blocked replication of SARS and MERS, sister coronaviruses to SARS-CoV-2, the coronavirus causing the current outbreak. Based on this data, scientists and physicians thought that it had a good chance of being effective against the novel coronavirus. Remdesivir is not currently approved in any country to treat any condition.
In a press release, Merdad Parsey, MD, PhD, Gilead’s chief medical officer, acknowledged the shortcomings of the study, stating, “While the outcomes observed in this compassionate use analysis are encouraging, the data are limited. Gilead has multiple clinical trials underway for remdesivir with initial data expected in the coming weeks.”
The biggest critique of the compassionate use research is that Gilead cherry-picked the patients who would receive the drug. To be eligible, people must have a positive test for SARS-CoV-2 and either an oxygen saturation level below 95% or be on oxygen support, such as a ventilator. They also must not be in kidney or liver failure or have problems with blood pressure. According to the press release, 1,800 patients have been treated with remdesivir under compassionate use. However, there is no information about how many requests Gilead received or how many requests were granted.
Green says the kidney, liver, and blood pressure exclusion criteria are in place to protect patients because the side effects of the medication are still unknown. However, Schwartz is more critical, saying the requirements exclude the sickest patients who are least likely to recover, potentially biasing the data.
“It’s really walking quite a tightrope to only include patients that are on a ventilator, so they have respiratory failure but don’t yet have involvement of other organs,” Schwartz explains.
Schwartz says that most people progress from respiratory failure to multi-organ failure in 24 to 48 hours. If they don’t progress, they are more likely to get better. “These are the ones that have been cherry-picked,” he says.
“I find it crazy that it has to be such a process to gain these types of resources that could potentially save people’s lives.”
Gilead has since stopped the compassionate use program of remdesivir except for pregnant women and children under the age of 18. In its place, they have launched an expanded access program to deliver the drug to people who can’t be enrolled in the clinical trials either because of geography or the exclusion criteria. The program is supposed to more efficiently administer the drug to more patients. However, according to clinicaltrials.gov, at the time of publication, there are only 19 expanded access sites in eight states, several of which are hospitals that are also part of the clinical trial. Consequently, the new program leaves many patients, especially those being treated in rural areas, in the lurch.
Peter Jardine, a 58-year-old mechanical engineer from South Berwick, Maine, is one of those patients. Jardine first started showing symptoms of Covid-19 on March 19. A week after he fell ill, he was admitted to York Hospital in Maine with shortness of breath and a fever of over 104 degrees. The next day, his coronavirus test results came back positive, and he was intubated as his oxygen levels plummeted. The doctors diagnosed him with acute respiratory distress syndrome, a serious side effect of Covid-19, and transferred him to the Maine Medical Center intensive care unit.
Jardine’s doctors at Maine Medical Center recommended that he receive remdesivir to try to stem the infection, but the closest hospital with either a clinical trial or expanded access was in Boston, over 100 miles away. His family petitioned the governor of Maine to intervene on his behalf, but their pleas for compassionate use were unsuccessful. In the days since, Jardine has been put on dialysis to support his failing kidney function, which disqualifies him for the drug.
“I find it crazy that it has to be such a process to gain these types of resources that could potentially save people’s lives,” his daughter Ashley Jardine told Elemental. “I understand sometimes these things can be a process, but 4,000 doses were just delivered to New York City hospitals, so why not us? Why not everywhere?”
Schwartz, whose hospital in Canada has also been denied requests for remdesivir, says that Gilead’s exclusion criteria and their roll out of the drug are “frustrating and hamstrings access.” He says that even though they have no idea whether the drug is “helpful or harmful, there is a tendency for [doctors] to want to do something and to treat, even though you don’t have any evidence of the actual benefit.”
Update 4/16/20: In an email to Elemental, Ashley Jardine reports that her father, Peter Jardine, has been taken off of ventilation and is expected to make a full recovery. He never received remdesivir, but Maine Medical Center, where Jardine is still being treated, is now included in Gilead’s clinical trial. Three Covid-19 patients there (including Ashley’s maternal grandmother) have received the drug so far.