APhA coronavirus watch: Patients with COVID-19 recover more quickly with remdesivir treatment, clinical trials show

A 5-day course of the investigational antiviral drug remdesivir led to greater clinical improvement for patients with moderate and severe COVID-19 disease in two Phase III SIMPLE trials, according to Gilead Sciences in a June 1 news release. Gilead’s findings support the preliminary results of the Adaptive COVID-19 Treatment Trial (ACTT-1) published in the May 27 issue of the New England Journal of Medicine, which showed that remdesivir was superior to placebo in shortening the time to recovery in adults hospitalized with COVID-19.

“We now have three randomized, controlled clinical trials demonstrating that remdesivir improved clinical outcomes by several different measures,” stated Merdad Parsey, MD, PhD, chief medical officer of Gilead, in the news release. “The additional data we have in hand today will further guide our research efforts, including evaluating treatment earlier in the course of disease, combination studies with other therapies for the most critically ill patients, pediatric studies and the development of alternate formulations.”

SIMPLE trials

Both SIMPLE studies are randomized, open-label, multicenter trials in countries with a high prevalence of COVID-19 infections. Clinical improvement was defined as an improvement of 2 or more points from baseline on a predefined 7-point scale, ranging from hospital discharge to increasing levels of oxygen support to death. Patients achieved clinical recovery if they no longer required oxygen support and medical care or were discharged from the hospital.

In the initial phase of the first SIMPLE trial, researchers randomized 397 patients with severe disease to receive a 5- or 10-day treatment course of remdesivir in addition to standard of care. An expansion phase of the study was added to enroll up to 5,600 additional patients, including those on mechanical ventilation.

The time to clinical improvement for 50% of patients was 10 days in the 5-day treatment group and 11 days in the 10-day treatment group. More than one-half of patients in both treatment groups were discharged from the hospital by day 14. At day 14, 64.5% of patients in the 5-day treatment group and 53.8% of patients in the 10-day treatment group achieved clinical recovery.

The initial phase of the second Phase II SIMPLE trial randomized 600 patients with moderate disease in a 1:1:1 ratio to receive either a 5-day or a 10-day treatment course of remdesivir in addition to standard of care, compared with standard of care alone. The secondary study objective was the rate of adverse events in each remdesivir treatment group compared with standard of care.

The results showed that patients in the 5-day treatment group were 65% more likely to have clinical improvement at day 11 compared with those in the standard of care group. The odds of improvement in clinical status with the 10-day treatment course of remdesivir versus standard of care were also favorable, trending toward but not reaching statistical significance.

Remdesivir was generally well tolerated in both treatment groups, with nausea, diarrhea, and headache the most common adverse events.

An expansion phase of the study was added to enroll up to 1,000 additional patients with moderate disease. Results from the expansion phase are expected in the coming months.

ACTT-1 trial

In the ACTT-1 trial, sponsored by the National Institutes of Health, Beigel and colleagues conducted a double-blind, randomized, placebo-controlled trial of I.V. remdesivir in adults hospitalized with Covid-19 with evidence of lower respiratory tract involvement. Patients were randomly assigned to receive either remdesivir at 200 mg loading dose on day 1, followed by 100 mg daily for up to 9 additional days or placebo for up to 10 days. The primary outcome was the time to recovery, defined by either discharge from the hospital or hospitalization for infection-control purposes only.

Preliminary results indicated that those who received remdesivir had a median recovery time of 11 days compared with 15 days in those who received placebo. The Kaplan-Meier estimates of mortality by 14 days were 7.1% with remdesivir and 11.9% with placebo.

EUA

FDA granted remdesivir an Emergency Use Authorization (EUA) on May 1 for the treatment of hospitalized patients with severe COVID-19. Gilead encourages health care providers to review the accompanying fact sheets on the authorized use of remdesivir and mandatory requirements of the EUA, which can be accessed at www.gilead.com/remdesivir.