CLINICAL TRIAL RESULTS

Remdesivir is an unapproved antiviral drug with available data from two randomized clinical trials and a compassionate use program in patients with COVID-19, and from clinical trials in healthy volunteers and subjects with Ebola virus disease.

Clinical Trials in Subjects with COVID-19

NIAID ACTT-1 Study

A randomized, double-blind, placebo-control clinical trial evaluated remdesivir 200 mg once daily for 1 day followed by remdesivir 100 mg once daily for 9 days (for a total of up to 10 days of intravenously administered therapy) in hospitalized adult patients with COVID-19. The trial enrolled 1063 hospitalized patients in a 1:1 manner to receive remdesivir or placebo. The primary clinical endpoint was time to recovery within 28 days after randomization. In a preliminary analysis of the primary endpoint performed after 606 recoveries were attained, the median time to recovery was 11 days in the remdesivir group compared to 15 days in the placebo group (hazard ratio 1.31; 95% CI 1.12 to 1.54, p<0.001). Mortality was 8.0% for the remdesivir group versus 11.6% for the placebo group (p = 0.059).

Study GS-US-540-5773

A randomized, open-label multicenter clinical trial (Study GS-US-540-5773) of patients with severe COVID-19 compared 197 adult patients who received remdesivir 200 mg once daily followed by remdesivir 100 mg once daily for 9 days (for a total of 10 days of intravenously administered therapy) with 200 adult patients who received remdesivir 200 mg once daily followed by remdesivir 100 mg for 4 days (for a total of 5 days of intravenously administered therapy), plus standard of care. The primary clinical endpoint was clinical status assessed by a 7-point ordinal scale on Day 14 after randomization. The study suggested that patients receiving a 10-day treatment course of remdesivir had similar improvement in clinical status compared with those receiving a 5-day treatment course (10-to-5-day odds ratio: 0.76; 95% confidence interval [CI] 0.51 to 1.13] on Day 14).

Clinical improvement was defined as an improvement of two 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 or were discharged from the hospital. 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. At Day 14, observed rates between the 5- and 10-day treatment groups were 65% vs 54% for clinical improvement, 70% vs 59% for clinical recovery, and 8% vs 11% for mortality.

Compassionate Use Program in Patients with COVID-19

Remdesivir has been provided through a compassionate use multicenter, open-label program to over 1,200 adult patients with confirmed SARS-CoV-2 infection by polymerase chain reaction (PCR) and manifestations of severe disease. In addition, remdesivir has been provided to 76 pediatric patients <18 years of age and 96 pregnant women through the compassionate use program.

Patients were treated with remdesivir 200 mg once daily followed by remdesivir 100 mg for 9 days intravenously, plus standard of care, for a total of up to 10 days of therapy.

Clinical Studies in Healthy Adults

Remdesivir was evaluated in four Phase 1 studies in 138 healthy adult volunteers

(Studies GS-US-399-1812, GS-US-399-1954, GS-US-399-4231, and GS-US399-5505). In these studies, transient graded elevations in ALT and AST were observed at repeated once-daily doses of remdesivir.

Clinical Study in Subjects with Ebola Virus Disease

Supportive safety data are provided from the PALM study, a Phase 2/3, open-label, randomized, parallel-group study to assess the safety and efficacy of investigational treatments, including remdesivir, in patients with Ebola virus disease. 175 patients were randomized to receive remdesivir. A total of 9 SAEs judged by the site investigator as not related to the underlying Ebola virus disease were reported for participants receiving remdesivir. Of these, an event of hypotension, which occurred during the administration of the loading dose and led to fatal cardiac arrest, was considered related to remdesivir. The independent pharmacovigilance committee noted that the death could not be readily distinguished from underlying fulminant Ebola virus disease.

DESREM™, Remdesivir Prescribing Information. Mylan Laboratories Limited. 2020.