FDA Issues EUA for Remdesivir After Trio of Studies

The US Food and Drug Administration (FDA) has issued an emergency use authorization of the antiviral drug remdesivir for the treatment of patients with coronavirus 2019 (COVID-19).

The decision comes just days after clinicians were hit with a wave of new information from an array of trials assessing the drug in patients with COVID-19. The results indicate mixed findings for benefit, but ended on an optimistic note.

The initial data released Wednesday were shared by Gilead, and were overall positive. Then the second results, from a study in Hubei, China, cast doubt on efficacy.

By the end of the day, however, remdesivir had the praise of National Institutes of Allergy and Infectious Diseases (NIAID) director Anthony Fauci, MD, who told reporters that preliminary results of another trial—overseen by NIAID—could make the antiviral a "standard of care," although the data still need to be properly peer reviewed.

Sponsored by NIAID, the Adaptive COVID-19 Treatment Trial (ACTT) is a randomized, controlled trial evaluating remdesivir compared with placebo in 1063 patients from 68 sites (47 US and 21 countries in Europe and Asia). Participants include patients with advanced COVID-19 who exhibit evidence of lung involvement, including rattling sounds when breathing with a need for supplemental oxygen or abnormal chest X-rays, or illness requiring mechanical ventilation.

"Patients who received remdesivir had a 31% faster time to recovery than those who received placebo (p<0.001)," NIAID said in a press release. "Specifically, the median time to recovery was 11 days for patients treated with remdesivir compared with 15 days for those who received placebo. Results also suggested a survival benefit, with a mortality rate of 8.0% for the group receiving remdesivir versus 11.6% for the placebo group (p=0.059)."

“It’s quite good news,” Fauci said regarding the NIAID study. “[The 31% faster time to recovery versus placebo] is very important. This is a drug that can block the virus.”

Earlier, Gilead had released topline results from their open-label, phase 3 SIMPLE trial of remdesivir in patients hospitalized with the virus. Investigators compared five-day and 10-day dosing regimens of the investigative antiviral drug. Similar improvement was observed in five-day dose patients (OR, 0.75; 95% CI, 0.51-1.12 at Day 14) compared to 10-day dose patients.

Half of the five-day patients reported a time to clinical improvement of 10 days, and a majority of patients in both treatment groups were discharged from the hospital in 14 days (P = .14)

Participants who received remdesivir within the first 10 days of symptom onset had improved outcomes relative to those treated after 10-plus days of symptoms. Pooling data across treatment arms, 62% of patients treated within 10 days were able to be discharged from the hospital, versus just 49% of patients who were treated late.

Lead investigator Aruna Subramanian, MD, clinical professor of Medicine at Stanford University, said additional data is still needed for the ongoing, 5600-patient trial—but the current results show a better understanding of optimal remdesivir treatment duration.

Another study published online in The Lancet shortly following the Gilead release showed adult hospitalized patients treated with the intravenous drug in Hubei, China over 10 days did not report consistently beneficial outcomes.

In assessing time to clinical improvement from baseline to 28 days post-randomization in the double-blind, placebo-controlled trial, investigators did not find an associated improvement with remdesivir (HR, 1.23; 95% CI, 0.87-1.75).

Another two-thirds (n = 102 [66%]) of remdesivir-treated patients reported adverse events, and 12% stopped treatment early, versus 64% and 5% of patients on placebo, respectively.

Though it was considered statistically insignificant, investigators did report a faster time to clinical improvement in treated patients versus placebo (HR, 1.52; 95% CI, 0.95-2.43). Among the observed limitations to the one-month trial was the initiation of remdesivir late into COVID-19 disease course among treated patients.

Investigators suggested their assessment be replicated among larger patient populations to better inform the effect of remdesivir.

“Furthermore, strategies to enhance the antiviral potency of remdesivir (eg, higher-dose regimens, combination with other antivirals, or SARS-CoV-2 neutralising antibodies) and to mitigate immunopathological host responses contributing to COVID-19 severity (eg, inhibitors of IL-6, IL-1, or TNFα) require rigorous study in patients with severe COVID-19,” they concluded.

In an interview this week regarding the proscpect of a remdesivir EAU, Contagion Editor in Chief Jason C. Gallagher, PharmD, clinical professor at Temple University College of Pharmacy, called the decision influential on many facets of COVID-19 care—from redefining standard of care, to treatment costs and clinical trial enrollment.

"Once the horse is out of the barn, we’re going to have to manage everything based upon what people are going to see as a new standard," Gallagher said.

He added that, until now, the greatest driver of actual COVID-19 treatment has been clinical trial enrollment.

"And now that there’s actually a therapeutic available, obviously that’s going to be key," Gallagher said. "How we steward that, how it’s going to be available—these are all questions that I have."