5 Questions About Remdesivir Answered
You’ve probably heard about the COVID-19 treatment that’s being used with some success in severely ill coronavirus patients. Here’s the latest on how—and if—it works.
There’s been much talk of late about the medication remdesivir, which many Americans are grasping onto as a glimmer of hope in the fight against the COVID-19 pandemic. Patients in the U.S. who are severely ill with the novel coronavirus may now be given this drug, an investigational antiviral therapy that has shown potential as an effective treatment.
Remdesivir hadn’t previously been approved by the U.S. Food and Drug Administration (FDA) for any purpose. The FDA issued an emergency use authorization (EUA) of the drug on May 1 after reviewing preliminary research sponsored by the National Institute of Allergy and Infectious Diseases (NIAID). What's important to remember? An EUA is not the same as an official approval. Instead, it gives doctors permission to prescribe the drug while further research continues.
So far, the data show that remdesivir has the potential to shorten the duration of illness in severely ill COVID-19 patients and reduce hospitalizations by up to four days. Anthony Fauci, M.D., director of NIAID, has said that the study shows “a clear-cut, significant, positive effect in diminishing the time to recovery.”
Still, it's early days. Here's what we know right now:
What is remdesivir and how does it work?
Remdesivir, manufactured by the California-based pharmaceutical company Gilead Sciences, was developed as a possible treatment for the Ebola virus back in 2014, but other medications were found to be more effective. But it hasn’t simply sat on a shelf collecting dust. Before COVID-19 hit, remdesivir was studied in animals as a potential treatment for two other coronaviruses, severe acute respiratory syndrome (SARS) and Middle East respiratory syndrome (MERS). The drug was effective in in-vitro lab tests and animals, but it wasn’t tested in humans because researchers didn’t have access to enough potential study participants.
The drug is given to COVID-19 patients intravenously. Remdesivir has been shown to block the virus from making a specific enzyme that it needs for replication. “It interrupts the virus’s ability to multiply,” says William Schaffner, M.D., medical director of the National Foundation for Infectious Diseases and professor of infectious diseases at Vanderbilt University’s School of Medicine in Nashville.
That said, we still don't know exactly how effective the drug is in humans nor do doctors have a good handle on potential side effects. Those are important questions the continuing research will help answer. Some patients who received remdesivir did report experiencing nausea, vomiting, chills, low blood pressure, and/or a rise in liver enzyme levels, which may mean that their liver has become inflamed or that liver cells have been damaged. But since so few people have been treated with the drug thus far, that list could grow longer. It’s also unknown whether side effects could be more pronounced among people with chronic conditions, such as rheumatoid arthritis, cardiovascular disease, and multiple sclerosis, for example.
In terms of possible side effects, "we will learn as we go,” says Kamlendra Singh, Ph.D., research assistant professor of molecular microbiology and immunology at the University of Missouri Bond Life Sciences Center in Columbia, MO.
With so many unknowns, why did the FDA grant it emergency approval?
It comes down to a pretty simple risk-benefit analysis. More than 82,000 Americans have died so far from COVID-19 with more losing their lives every day. No other treatments exist. And while scientists don't have all the answers on remdesivir yet, they've got a solid foundation to guide them:
Within the NIAID-sponsored study of 1,063 patients, those who were treated with remdesivir intravenously for 10 days recovered 31% faster than patients who received placebo. That means they were able to leave the hospital after an average of 11 days, rather than 15 days. And fewer severely ill patients with COVID-19 died when receiving remdesivir (8%) than placebo (11.6%) during the study.
“[Remdesivir use] seemed to show that it could reduce the duration of hospitalization, and there was a trend toward improved survival, all of which is quite optimistic,” says Dr. Schaffner.
Another study that launched in January 2020 analyzed remdesivir use in 53 hospitalized patients with severe COVID-19. Results showed that 68% of patients who received the drug were able to breathe more easily, and 57% of patients who were on ventilators were able to breathe again on their own, according a report published in April in the New England Journal of Medicine. In addition, 47% of patients who received the drug were able to leave the hospital during the study.
A third study, this one published in April 2020 in the journal Pathogens, found that four antiviral drugs, including remdesivir, were all effective at stopping the virus from replicating. (The other three drugs were 5-fluorouracil, ribavirin, and favipiravir.) “I don’t know which one will work better, but we do have options,” says Dr. Singh, who authored that study. “The idea was to put these drugs that are already there out to the public and to the doctors and say, ‘Look, we have these options, and we should use them.’”
It's research like this that helped the experts at the FDA make the call: “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 letter granting emergency use authorization. Not very flashy or exciting, but clear in its intent.
Can people in the hospital with COVID-19 right now get remdesivir?
In a word ... maybe.
In early May, Gilead donated its entire supply of remdesivir to the federal government so that it could be used to treat patients. The stash includes 1.5 million doses of the drug—enough to treat 140,000 patients, if each patient receives the medication for 10 days. The company has since sped up its manufacturing process to increase the drug supply quickly.
Remdesivir was initially distributed to states with high numbers of COVID-19 cases, including New York, New Jersey, Massachusetts, and Illinois, but the medication will “soon” be distributed—the official government language is vague—to all 50 states, according to a press release from the U.S. Department of Health and Human Services’ Office of the Assistant Secretary for Preparedness and Response.
Experts hope that remdesivir will help fight COVID-19 on a widespread scale. The possible impact the drug may have on people with certain chronic conditions remains an open question mark, but until another treatment emerges, doctors may rely upon remdesivir as their best option.
“Physicians around the country now can try to access that drug for the benefit of their patients,” Dr. Schaffner says.
What questions will researchers try to answer next about remdesivir?
To date, remdesivir studies have focused on severely ill, hospitalized patients. More research needs to be done to determine whether the medication may be helpful to patients at earlier stages of the disease as well as whether this early treatment can prevent the most serious complications of COVID-19—silent hypoxia, abnormal blood-clotting, and stroke—from developing.
“If remdesivir affects virus multiplication, it would probably work better if it were used earlier in the infection, rather than later,” Dr. Schaffner says. “Later, much of the damage [within the body] is caused by the body’s inflammatory response.” The theory is that the sooner that process is interrupted, the less likely it is to become life-threatening. For now, all we can do is wait to see what the science bears out.
What other drugs are being studied?
While some severely ill patients are receiving remdesivir, researchers are studying the effectiveness of other drugs to fight COVID-19, too.
“There are something like a 180-plus clinical trials of one kind or another going on around the world trying to assess the effectiveness of an array of treatments,” Dr. Schaffner says.
The anti-cancer drug gemcitabine may be effective against COVID-19, says Dr. Singh, because it has been shown to be effective against other coronaviruses. “One of my collaborators [tested] which drugs can work against MERS coronavirus,” he adds. “He did find that one of the drugs that came out upstream was gemcitabine. So, I think that might work, too.”
Researchers at Emory University are studying the effects of baricitinib, an anti-inflammatory drug used to treat rheumatoid arthritis, used in combination with remdesivir in hospitalized COVID-19 patients. A Phase 3 clinical trial of the drug began in June, with up to 400 hospitalized adults with COVID-19 expected to participate before it’s concluded.
The drugs hydroxychloroquine and chloroquine were also briefly used to treat COVID-19, although the FDA warned they should not be considered outside of clinical studies because they've been linked with serious heart problems among COVID-19 patients. While both treatments received a EUA back in late March, this special clearance was revoked in mid-June based on the FDA’s continued review of the scientific evidence available. There is no conclusive data suggesting these drugs have a beneficial effect against the virus—and in fact, they may do harm in some patients.
As for now, remdesivir remains our best—and, at this point, only—available treatment in the pandemic fight (although the cheap, easily assessible corticosteroid dexamethasone has shown promise in helping tame dangerous inflammation, too). “I have cautious optimism,” Dr. Schaffner says. “[The NIAID-sponsored study] was a very rigorous trial, and it did show that people stayed in the hospital for a shorter period of time, on average. That’s a very good result, [but] we don’t have the complete results of that trial available yet.”
Even while patients receive remdesivir, it’s still crucial to continue developing other treatments. “I have feeling that [remdesivir] should work, but based on the analysis, I think the virus will mutate eventually,” Dr. Singh warns. “We still have to look for other options.”
Remdesivir Emergency Use Authorization, Remdesivir Side Effects: U.S. Food and Drug Administration. (May 1, 2020.) “Coronavirus (COVID-19) Update: FDA Issues Emergency Use Authorization for Potential COVID-19 Treatment.” fda.gov/news-events/press-announcements/coronavirus-covid-19-update-fda-issues-emergency-use-authorization-potential-covid-19-treatment
Remdesivir and COVID-19 Preliminary Study Results: National Institutes of Health. (April 29, 2020.) “NIH clinical trial shows Remdesivir accelerates recovery from advanced COVID-19.” nih.gov/news-events/news-releases/nih-clinical-trial-shows-remdesivir-accelerates-recovery-advanced-covid-19
Remdesivir Background: Gilead Sciences, Inc. (n.d.) “Development of remdesivir.” gilead.com/-/media/gilead-corporate/files/pdfs/covid-19/gilead_rdv-development-fact-sheet-2020.pdf
Remdesivir Mechanism: Journal of Biological Chemistry. (April 13, 2020.) “Remdesivir is a direct-acting antiviral that inhibits RNA-dependent RNA polymerase from severe acute respiratory syndrome coronavirus 2 with high potency.” jbc.org/content/early/2020/04/15/jbc.RA120.013679
Remdesivir Strategies: Military Medical Research. (May 5, 2020.) “Role of adjunctive treatment strategies in COVID-19 and a review of international and national clinical guidelines.” ncbi.nlm.nih.gov/pmc/articles/PMC7199873/
Remdesivir Use: New England Journal of Medicine. (April 10, 2020.) “Compassionate Use of Remdesivir for Patients with Severe Covid-19.” nejm.org/doi/10.1056/NEJMoa2007016
Remdesivir and Placebo: The Lancet. (April 29, 2020.) ““Remdesivir in adults with severe COVID-19: a randomised, double-blind, placebo-controlled, multicenter trial.” thelancet.com/journals/lancet/article/PIIS0140-6736(20)31022-9/fulltext
Remdesivir as Treatment: Pathogens. (April 26, 2020.) “Feasibility of Known RNA Polymerase Inhibitors as Anti-SARS-CoV-2 Drugs.” mdpi.com/2076-0817/9/5/320
Remdesivir and Baricitinib: Emory University. (May 8, 2020.) “Emory, Lilly, NIAID join academic centers in clinical trial to demonstrate efficacy of remdesivir and baricitinib against COVID-19.” news.emory.edu//stories/2020/05/coronavirus_remdesivir_baricitinib_against_covid19/index.html
Hydroxychloroquine and Chloroquine: U.S. Food and Drug Administration. (n.d.) “FDA cautions against use of hydroxychloroquine or chloroquine for COVID-19 outside of the hospital setting or a clinical trial due to risk of heart rhythm problems.” fda.gov/drugs/drug-safety-and-availability/fda-cautions-against-use-hydroxychloroquine-or-chloroquine-covid-19-outside-hospital-setting-or
Remdesivir Production and Distribution: Gilead Sciences, Inc. (May 1, 2020.) “Gilead’s Investigational Antiviral Remdesivir Receives U.S. Food and Drug Administration Emergency Use Authorization for the Treatment of COVID-19.” gilead.com/news-and-press/press-room/press-releases/2020/5/gileads-investigational-antiviral-remdesivir-receives-us-food-and-drug-administration-emergency-use-authorization-for-the-treatment-of-covid19