By Jonathan Springston, Editor, Relias Media
The results from a pair of investigations revealed the potential efficacy of the antiviral drug remdesivir against COVID-19.
In the United States, preliminary data from the National Institute of Allergy and Infectious Diseases’ (NIAID) Adaptive COVID-19 Treatment Trial has emerged. Among 1,063 patients enrolled in the randomized, controlled trial (which started on Feb. 21), patients who took remdesivir recovered 31% faster than those who received placebo (P < 0.001). The median time to recovery was 11 days for remdesivir patients vs. 15 days for placebo patients (mortality rate, 8% for remdesivir vs. 11.6% for placebo; P = 0.059).
Shortly after the release of these data, NIAID Director Anthony Fauci, MD, during a briefing with reporters at the White House, said this information is “highly significant” and indicates remdesivir produces a “clear-cut, significant, positive effect in diminishing the time to recovery.”
Additionally, a group of investigators recently published a much more detailed report on the results of a randomized, double-blind, placebo-controlled, multicenter trial conducted at 10 hospitals in Hubei, China. Between Feb. 6 and March 12, the authors randomized 237 adult patients to remdesivir or placebo. Eligible patients had been admitted to a hospital with laboratory-confirmed COVID-19, with an interval from symptom onset to enrollment of 12 days or less, oxygen saturation of 94% or less on room air or a ratio of arterial oxygen partial pressure to fractional inspired oxygen of 300 mm Hg or less, and radiologically confirmed pneumonia.
The authors observed patients who took remdesivir exhibited a numerically faster time to clinical improvement than those on placebo among patients with symptom duration of 10 days or less, although researchers did not consider this statistically significant. Of concern, adverse events were reported in 102 of 155 remdesivir patients, and the authors ended remdesivir treatment early because of adverse events in 18 patients vs. four patients who stopped taking placebo early.
“We found that this dose regimen of intravenous remdesivir was adequately tolerated but did not provide significant clinical or antiviral effects in seriously ill patients with COVID-19. However, we could not exclude clinically meaningful differences and saw numerical reductions in some clinical parameters,” the authors concluded. “Ongoing studies with larger sample sizes will continue to inform our understanding of the effect of remdesivir on COVID-19.” (This accompanying editorial explains in much more detail the strengths and weaknesses of this investigation.)
These are just two of the many trials of remdesivir and its effect on COVID-19 that are underway or recruiting participants. Meanwhile, it feels like momentum is building behind the drug.
In early March, Gilead Sciences, the maker of remdesivir, applied for and was granted an orphan drug designation, which the U.S. Food and Drug Administration (FDA) grants to a drug that treats a disease that affects fewer than 200,000 people in the United States. The designation provides several benefits to the drug manufacturer, including tax credits, waived fees, and marketing exclusivity.
However, shortly after receiving it, Gilead asked the FDA to rescind the designation, stating, “Gilead is confident that it can maintain an expedited timeline in seeking regulatory review of remdesivir, without the orphan drug designation. Recent engagement with regulatory agencies has demonstrated that submissions and review relating to remdesivir for the treatment of COVID-19 are being expedited.”
Flash forward two months, when the Japanese government authorized remdesivir as the nation’s first official treatment for COVID-19. That announcement arrived just days after the FDA issued an emergency use authorization for the drug.
“Based on evaluation of the emergency use authorization criteria and the scientific evidence available, it was determined that it is reasonable to believe that remdesivir may be effective in treating COVID-19, and that, given there are no adequate, approved, or available alternative treatments, the known and potential benefits to treat this serious or life-threatening virus currently outweigh the known and potential risks of the drug’s use,” the agency said.
Now, Gilead has outlined its plan to ramp up production and distribution of remdesivir, which includes forming international partnerships around supply chain management and entering into various licensing agreements.
“Gilead is working to build a consortium of manufacturing partners, to bring efforts together to help maximize global supply,” the company announced this week. “Producing the drug requires scarce raw materials, with their own lengthy production time, and specialized manufacturing capabilities with limited global capacity. Any disruption to the supply chain impacting these scarce raw materials and other manufacturing inputs could reduce the amount of remdesivir produced and increase the time it takes to do so.”
Of note, there are U.S. clinicians already expressing concern about which facilities will receive remdesivir, why or why not, and who oversees such decisions. This, on top of ongoing questions about Gilead's pricing tactics and the company's recent entanglement with the federal government over alleged patent infringements
Certainly, remdesivir is receiving plenty of buzz today, but it is far from the only therapeutic under investigation. The World Health Organization’s International Clinical Trials Registry Platform reveals the eye-popping extent of this work.
As more clinical trial data are published, be sure to read the latest issues of Internal Medicine Alert and Infectious Disease Alert to learn more. For all the latest Relias Media COVID-19 coverage, click here.