Remdesivir Benefits Less Clear in Patients With Moderate COVID-19 Pneumonia

While remdesivir is definitely beneficial for hospitalized patients with severe COVID-19, the advantages are less clear-cut for patients hospitalized with moderate pneumonia related to novel coronavirus infection. Find out what a new study determined when comparing patients receiving both a 5-day and 10-day course of remdesivir to those receiving standard care.

FOSTER CITY, CA – While remdesivir showed clinically meaningful benefit in patients with severe COVID-19, its efficacy was less clear in those hospitalized with more moderate COVID-19-related pneumonia.

A report in JAMA described the results of a randomized, open-label, phase 3 trial of that included 584 patients with moderate COVID-19. While Gilead Sciences-led researchers note that the day 11 clinical status distribution measured on a 7-point ordinal scale was significantly better for those randomized to a 5-day course of remdesivir – a median length of treatment of 5 days -- compared with those randomized to standard care, the difference for those randomized to a 10-day course – a median length of treatment of 6 days -- compared with standard care was not significantly different.

“Hospitalized patients with moderate COVID-19 randomized to a 5-day course of remdesivir had a statistically significantly better clinical status compared with those randomized to standard care at 11 days after initiation of treatment, but the difference was of uncertain clinical importance,” researchers write.

The trial was initiated because remdesivir, a nucleotide prodrug whose active metabolite inhibits viral RNA-dependent RNA polymerases, demonstrated clinical benefit in a placebo-controlled trial in patients with severe coronavirus disease 2019.

The goal was to determine the efficacy of 5 or 10 days of remdesivir treatment compared with standard care on clinical status on day 11 after initiation of treatment.

Included in the trial were hospitalized patients with moderate COVID-19 pneumonia, defined as pulmonary infiltrates and room-air oxygen saturation greater than 94%. Participants were enrolled from March 15 through April 18, 2020, at 105 hospitals in the United States, Europe, and Asia, with May 20, 2020, being the date of final follow-up.

Patients were randomized to either:

• a 10-day course of remdesivir (n = 197),
• a 5-day course of remdesivir (n = 199), or
• standard care (n = 200).

Remdesivir was dosed intravenously at 200 mg on day 1 followed by 100 mg/d.

The study used a 7-point ordinal scale ranging from death (category 1) to discharged (category 7). The primary end point was defined as clinical status on day 11.

Of the 584 patients who began the study and received remdesivir or continued standard care, the median age was 57, 39% were women, 56% had cardiovascular disease, 42% hypertension, and 40% diabetes; most, 91% completed the trial.

Researchers report that, on day 11, patients in the 5-day remdesivir group had statistically significantly higher odds of a better clinical status distribution than those receiving standard care (odds ratio, 1.65; 95% CI, 1.09-2.48; P = .02). On the other hand, the clinical status distribution on day 11 between the 10-day remdesivir and standard care groups was not significantly different (P = .18 by Wilcoxon rank sum test).

By day 28, nine patients had died: 2 (1%) in the 5-day remdesivir group, 3 (2%) in the 10-day remdesivir group, and 4 (2%) in the standard care group. Side effects more frequent among patients receiving remdesivir than standard care were nausea (10% vs 3%), hypokalemia (6% vs 2%), and headache (5% vs 3%).

“Among patients with moderate COVID-19, those randomized to a 10-day course of remdesivir did not have a statistically significant difference in clinical status compared with standard care at 11 days after initiation of treatment,” the authors conclude. “Patients randomized to a 5-day course of remdesivir had a statistically significant difference in clinical status compared with standard care, but the difference was of uncertain clinical importance.”

A randomized, double-blind clinical trial published in May found that patients with severe COVID-19 treated with a 10-day course of remdesivir had a significantly shorter time to recovery than those receiving placebo (11 days vs 15 days). Then, a randomized, open-label trial showed that patients with severe COVID-19 with relative hypoxia or requiring oxygen support but not requiring ventilatory support had outcomes with 5- and 10-day courses of remdesivir that were not significantly different.

That led to the Food and Drug Administration to grant Emergency Use Authorization of remdesivir for patients with severe COVID-19 and the European Medicines Agency to grant conditional marketing authorization to remdesivir for treatment of COVID-19 in patients 12 years of age or older with pneumonia who require supplemental oxygen.