Last week saw three studies with seemingly contradictory results about the antiviral drug remdesivir, culminating in the Food and Drug Administration (FDA) granting Emergency Use Authorization (EUA). What happened, exactly?
Until last weekend, treatment for COVID-19 was primarily experimental. In hundreds of clinical trials across the globe, researchers are testing new drugs, as well as those that scientists created for other purposes, to stem the death toll the world is facing.
On March 28, 2020, the FDA gave permission to doctors to use hydroxychloroquine sulfate and chloroquine phosphate products for the treatment of COVID-19 in adolescents and adults in situations where clinical trials were not an option.
Despite the hype around these drugs, the FDA followed up with an announcement on April 24, 2020, to highlight that they were investigating reports that some people had developed serious heart rhythm problems in response to the drugs.
“Hydroxychloroquine and chloroquine have not been shown to be safe and effective for treating or preventing COVID-19. They are being studied in clinical trials for COVID-19, and we authorized their temporary use during the COVID-19 pandemic for treatment of the virus in hospitalized patients when clinical trials are not available, or participation is not feasible, through an [EUA],” the FDA statement reads.
Much attention has since focused on a drug called remdesivir.
Pharmaceutical company Gilead Sciences, Inc. developed remdesivir as part of their antiviral drug portfolio to treat viral infections. This included work on coronaviruses.
Back in 2017, a team of researchers from the University of North Carolina at Chapel Hill and Vanderbilt University in Nashville, TN, published a study with Gilead in the journal Science Translational Medicine about remdesivir and coronaviruses.
“This drug was effective against multiple types of coronaviruses in cell culture[s] and in a mouse model of SARS and did not seem to be toxic,” the authors wrote in their paper. “Given its broad activity, this antiviral could be deployed to prevent spreading of a future coronavirus outbreak, regardless of the specific virus that jumps over.”
Gilead and the National Institutes of Health (NIH) also tested the drug in clinical trials for the treatment of Ebola, but they announced in August last year that two other drugs are more effective.
So, how does remdesivir work?
The answer to this question became clearer earlier this year, when a team from the University of Alberta in Edmonton, Canada — along with scientists from Gilead — published a paper in the Journal of Biological Chemistry.
Coronaviruses use an enzyme called RNA-dependent RNA polymerase to copy their genetic material when they replicate inside an infected cell. Remdesivir is a nucleotide analog, or a synthetic mimic of a naturally occurring molecule that viruses need for replication.
According to the researchers, remdesivir stops the replication process in their model of the coronavirus that causes MERS.
On February 25, 2020, the NIH began enrolling people into their remdesivir clinical trial to test the drug’s safety and efficacy in the treatment of COVID-19.
Several weeks earlier, researchers in China — along with international collaborators — started a separate trial of the drug in 10 hospitals in Hubei, China.
On April 23, 2020, news of the study’s failure began to circulate. It seems that the World Health Organization (WHO) had posted a draft report about the trial on their clinical trials database, which indicated that the scientists terminated the study prematurely due to high levels of adverse side effects.
The WHO withdrew the report, and the researchers published their results in The Lancet on April 29, 2020.
The number of people who experienced adverse side effects was roughly similar between those receiving remdesivir and those receiving a placebo. In 18 participants, the researchers stopped the drug treatment due to adverse reactions.
What did the results say about the efficacy of the drug for treating COVID-19?
“Remdesivir use was not associated with a difference in time to clinical improvement,” write the authors in the paper. They did highlight that people who had symptoms that lasted 10 days or under did recover faster, although these results were not statistically significant.
One caveat with their study was the number of participants; the researchers terminated the trial earlier than planned as they were unable to recruit any more volunteers.
“Our trial did not attain the predetermined sample size because the outbreak of COVID-19 was brought under control in China,” they explain.
However, also on April 29, 2020, the National Institute of