The FDA gave emergency use authorization (EUA) for remdesivir back in May, a step that allowed physicians to utilize the drug before researchers had completed rigorous testing. According to the National Institutes of Health, EUAs are issued when there is a reasonable belief that a medical product is going to be effective in treating a life-threatening illness. After three major studies demonstrated that remdesivir was both safe and effective in shortening recovery time for people hospitalized with COVID-19, the FDA issued its approval. “The drug can now be openly prescribed by healthcare providers for patients who are hospitalized with COVID-19 infection, so I think that’s definitely a step forward,” says Susan Kline, MD, MPH, a professor of medicine in the division of infectious diseases and international medicine at the University of Minnesota in Minneapolis, and a principal investigator for one of the studies. Here’s what you need to know about why the FDA approved remdesivir, who should take it, how it’s administered, and what patients can expect in terms of results and potential side effects.
Why Did the FDA Approve Remdesivir?
The FDA gave its approval to remdesivir after analyzing data from three randomized controlled clinical trials that included patients hospitalized with mild to severe COVID-19. In the largest study, which was published in October in the New England Journal of Medicine (NEJM) and included 1,062 individuals, scientists found that participants given remdesivir had their recovery shortened to a median of 10 days compared with 15 days for those who took a placebo. “We followed patients who were hospitalized with COVID-19 and had lower respiratory tract infection,” says Dr. Kline. “We definitely saw a benefit in time to recovery, which was defined as being ready to be discharged from the hospital or go home.” Data from this investigation also showed a a trend toward reduced mortality — meaning the drug seemed to lower the number of deaths — but the numbers were not statistically significant. Patients requiring low-flow oxygen at baseline who received remdesivir achieved a statistically significant 72 percent reduction in mortality at day 15 and a statistically significant 70 percent reduction in mortality at day 29.
Who Should Take Remdesivir?
Doctors can prescribe remdesivir to adults and young patients age 12 and up who are experiencing COVID-19 symptoms that are serious enough to require hospitalization. Patients must weigh at least 88 pounds, but doctors can request emergency use of the drug for younger and smaller patients while clinical trials are assessing its safety and effectiveness in that population. The FDA has identified hepatoxicity (a term used to describe liver injury) as the major risk of remdesivir use. This is why doctors monitor patients’ transaminase (enzyme) levels, as elevated liver enzymes can indicate liver damage. Remdesivir may also create problems for patients with kidney issues. “In some patients with low kidney filtration capacity, the drug could accumulate to levels which potentially could be harmful,” says Kline. “So it’s usually recommended that the medication not be given to patients with significantly decreased kidney function.” In addition, some people may experience hypersensitivity reactions related to how the drug is administered through an IV (delivering medication directly into a person’s vein). In some patients, the drug can also produce an anaphylactic (severe allergic) response. Signs and symptoms to watch out for include hypotension (abnormally low blood pressure), tachycardia (a fast heart rate), bradycardia (a slow heart rate), dyspnea (difficulty breathing), wheezing, angioedema (a rapid swelling beneath the skin), rash, nausea, vomiting, diaphoresis (unusual sweating), and shivering.
When Should a Patient Receive Remdesivir?
Kline says remdesivir will be prescribed when patients with COVID-19 are experiencing serious health problems, such as difficulty breathing. Albert Rizzo, MD, the chief medical officer of the American Lung Association and the chief of the pulmonary and critical care medicine section at Christiana Care Health System in Newark, Delaware, notes that the optimal time to administer remdesivir is not certain, but he believes patients may get the most benefit if they receive the medication before the point at which they may need mechanical ventilation. “I think certainly earlier is better when patients are starting to develop trouble with their breathing oxygen levels,” he says.
What Kind of Drug Is Remdesivir?
Gilead Sciences, the company that manufactures remdesivir, originally began developing the drug in 2009, and explored its use as treatment for Ebola in 2014. While the medication did not meet efficacy benchmarks in Ebola trials, those tests did show that the drug was safe to use in humans. Remdesivir is a nucleotide analog RNA polymerase inhibitor, meaning it works by blocking RNA polymerase — an enzyme that allows the virus’s RNA (a molecule essential to various biological roles) to replicate. “Remdesivir is classified as an antiviral because it really interferes with the [novel] coronavirus’s ability to regenerate once it gets into cells,” says Dr. Rizzo. “The cell is invaded by the coronavirus, which takes over the genetic system in the cell and starts replicating itself. But with remdesivir onboard, that duplicating process is disrupted because it affects the genetic reading of the virus’s code.”
How Is Remdesivir Administered?
Remdesivir is administered intravenously with an initial higher starting dose of 200 milligrams (mg) given on day 1 followed by once-daily maintenance doses of 100 mg (infused over 30 to 120 minutes) starting on day 2 and continuing for a total recommended duration of five days. Treatment can be extended up to 10 days if it isn’t effective after the initial five-day course. Ten days is the recommended duration for patients on a ventilator (which assists or replaces spontaneous breathing) or extracorporeal membrane oxygenation (ECMO), a life-support machine that replaces the function of the heart and lungs. It’s not clear that extending the amount of time a patient is on remdesivir confers any additional benefit; plus, there is the potential risk of increased side effects. “There is still a lot of uncertainty as to what the studies are exactly saying here,” Rizzo explains.
Where Do Doctors Administer Remdesivir?
Remdesivir is only to be administered in a hospital or in a healthcare setting capable of providing acute care comparable to inpatient hospital care. While Rizzo notes that it’s an unanswered question as to how available the medication will be, Kline says “there appears to be a good supply — there’s not a shortage.”
How Much Does Remdesivir Cost?
In a June press release, Gilead Sciences announced that the price of remdesivir for private insurance companies in the United States would be $520 per vial, meaning a standard five-day course of treatment would cost about $3,120. Gilead is charging a lower price of $390 per vial to the U.S. government, so for people enrolled in government programs a five-day course of treatment would cost $2,340. In August, a multi-state coalition urged Gilead to lower its prices for the drug. In a press release, the California Attorney General pointed out that the manufacturing cost of remdesivir is between $1 and $12 and called the set price “outrageous and unconscionable.”
How Conclusive Are the Studies on Remdesivir?
Although the FDA has approved remdesivir, the American Association for the Advancement of Science reported in its journal Science in October that the degree of benefit from remdesivir is still uncertain. A large study from the World Health Organization found that the drug did not reduce mortality or shorten recovery times in hospitalized patients. Matthew Heinz, MD, a hospitalist (hospital physician) in Tucson, Arizona who has treated COVID-19 patients with remdesivir, says that more research may be needed to understand the drug’s effectiveness. “Remdesivir is not something that we can say is a curative therapy,” Dr. Heinz states. “I would almost compare it to Tamiflu therapy for influenza — it reduces viral load and may reduce the length of the disease overall, and it seems to diminish the intensity of it, especially for those with a lot of comorbidities [two or more health conditions that occur in the same person at the same time].”
