The news coverage surrounding remdesivir, Gilead’s anti-viral drug, has been a bit of a roller coaster over the past few weeks. In mid-April, Gilead released preliminary results of a non-controlled trial of remdesivir for Covid-19 patients at a Chicago hospital, finding that nearly all patients with severe Covid-19 who were given the drug were discharged from the hospital in less than one week.
Then, a week later, leaked results from another remdesivir trial in China found that the drug was not effective in improving patients’ condition or preventing death from Covid-19, compared to a control group. However, this trial was ended prematurely due to not having enough patients.
But good news for Gilead came again with the results of the National Institutes of Health study of remdesivir, a randomized controlled trial with 1000+ patients. The NIH study found that patients with advanced Covid-19 who received the drug had a shorter time to recovery by 4 days compared to patients who received a placebo drug, which is a statistically significant result. White House health advisor Dr. Anthony Fauci declared that the trial “has proven is a drug can block this virus” and that remdesivir “will be the standard of care” for Covid-19 treatment.
Case closed, right? Not exactly. Since the release of these initial NIH study results, clinicians and researchers have posed many questions about remdesivir, which have so far gone unanswered. Here are a few of them:
Where is the full data set?
When the NIH released their clinical trial results, issued a press release with the top-level findings, but not the full comprehensive data set. Two weeks later, the report with full data is still not available.
“Rather than release information in dribs and drabs, study sponsors — whether a government, company, or university — should release all the results lickety-split,” writes pharmaceutical industry journalist Ed Silverman in a Stat News editorial.
Good news is sparse in the pandemic, and people understandably want to share the positive result of the remdesivir trial. But releasing the NIH study without the full data instantly turned remdesivir into the new standard of care, even though we don’t know about potential side effects, how the drug should best be allocated, or even whether the drug saves lives.
Does remdesivir improve survival?
If remdesivir helps patients recover from Covid-19 faster, that is a positive result. However, it is not the same as knowing whether remdesivir saves lives. The NIH results found that patients who took remdesivir were less likely to die than patients who recieved a placebo (8% vs 11.5%) but the difference was not statistically significant.
Unfortunately, this is all of the information clinicians and researchers have to go on, because the decided to stop the trial prematurely and start giving all trial participants remdesivir, before researchers could collect the information necessary to know whether or not the drug improves survival. Although some argue that the mortality results were “trending” toward significance, they could have just as easily been proved not significant with more data–we just don’t know.
Stopping the trial was undoubtably a tough ethical decision. But some experts are disappointed that the trial was stopped early. “Mortality is the right endpoint,” said Dr. Peter Bach, director of the Center for Health Policy and Outcomes at Memorial Sloan Kettering Cancer Center, in Stat News. “The reason we have shut our whole society down is not to prevent Covid-19 patients from spending a few more days in the hospital. It is to prevent patients from dying.”
How should this drug be used?
After the NIH study results were released, the US Food and Drug Administration acted fast to approve emergency use of remdesivir for Covid-19 patients, and the drug began to be distributed throughout the country. However, due to the absence of data, clinicians still have questions about which patients will receive the most benefit from the drug, and how the drug should be allocated.
The available clinical studies do not give clinicians enough information about which patients benefited most from the drug based on age or clinical severity. There is not enough remdesivir to give to all patients, but doctors do not know which patients to prioritize.
“In deciding who should receive this medication, how does one choose between, say, the 34-year-old health-care worker requiring oxygen support and the 65-year-old liver transplant recipient who has spent the past two weeks on a ventilator?” write doctors at Massachusetts General Hospital Mark Siedner, Alyssa Letourneau and Rochelle Walensky in an op-ed in The Washington Post.
The hype surrounding remdesivir and desperate situation of the pandemic, clinicians are under pressure to use the drug, but with basically no information to help them do this.
“In the wake of this media bombshell and data tease, we are left with a treatment that the FDA has permitted us to use, and that patients and families will justifiably expect, but with an extremely limited drug supply and no evidence-driven guidance on how to use it,” write Siedner et al.
Their conclusion: We need more data! Clinicians, researchers, and policymakers are relying on the full results of the NIH trial as well as new studies to guide their application of remdesivir–let’s hope this information arrives swiftly.