The investigational antiviral remdesivir “has a clear-cut, positive effect in diminishing the time to recovery” for patients infected with COVID-19, National Institute for Allergy and Infectious Diseases (NIAID) director Anthony Fauci said on Wednesday, announcing results of a phase 3 trial of the drug.
The Adaptive COVID-19 Treatment Trial (ACCT) found that hospitalized patients with advanced COVID-19 had a 31% faster time to recovery than those who received placebo (p<0.001). Specifically, the median time to recovery was 11 days for patients treated with remdesivir compared with 15 days for those who received placebo.
“This is really quite important for a number of reasons. Although a 31% improvement doesn’t seem like a knockout 100%, it is a very important proof of concept because what it has proven is a drug can block this virus,” Fauci said during a White House meeting on Apr 29.
Results of the ACCT trial also suggested a survival benefit, with a mortality rate of 8.0% for the group receiving remdesivir versus 11.6% for the placebo group.
Dr. Fauci says he was told data from a coronavirus drug trial testing Gilead’s remdesivir shows that “remdesivir has a clear cut significant, positive effect in diminishing the time to recovery.” https://t.co/kaovCY312w pic.twitter.com/cXcCcf750l— CNBC (@CNBC) April 29, 2020
The randomized, controlled trial involved 1063 patients and began on February 21. It is the first clinical trial launched in the United States to evaluate an experimental treatment for COVID-19.
An independent data and safety monitoring board (DSMB) noted that remdesivir was better than placebo from the perspective of the primary endpoint, time to recovery, a metric often used in influenza trials. Recovery in this study was defined as being well enough for hospital discharge or returning to normal activity level.
The first trial participant in the ACTT trial was an American who was repatriated after being quarantined on the Diamond Princess cruise ship that docked in Yokohama, Japan, and volunteered to participate in the study at the first study site, the University of Nebraska Medical Center/Nebraska Medicine, in February 2020. A total of 68 sites ultimately joined the study—47 in the United States and 21 in countries in Europe and Asia.
More detailed information about the trial results, including more comprehensive data, will be available in a forthcoming report.
Remdesivir, developed by Gilead Sciences Inc, is an investigational broad-spectrum antiviral treatment administered via daily infusion for 10 days.
TREATMENT DURATION (5-day vs 10-day)
Gilead also announced results of its open-label, Phase 3 SIMPLE trial evaluating 5-day and 10-day dosing durations of remdesivir in hospitalized patients with severe manifestations of COVID-19 disease.
The study demonstrated that patients receiving a 10-day treatment course of remdesivir achieved similar improvement in clinical status compared with those taking a 5-day treatment course. No new safety signals were identified with remdesivir across either treatment group, according to Gilead.
In this study, the time to clinical improvement for 50 percent of patients was 10 days in the 5-day treatment group and 11 days in the 10-day treatment group. More than half of patients in both treatment groups were discharged from the hospital by Day 14 (5-day: 60.0%, n=120/200 vs.10-day: 52.3% n=103/197; p=0.14). At Day 14, 64.5 percent (n=129/200) of patients in the 5-day treatment group and 53.8 percent (n=106/197) of patients in the 10-day treatment group achieved clinical recovery.
Key efficacy and safety results from the study are included in the table below.
|5-Day RDV (n=200)||10-Day RDV (n=197)||Baseline adjusted p-value1|
|Clinical Efficacy Outcomes at Day 14|
|≥ 2-point improvement in ordinal scale||129 (65)||107 (54)||0.16|
|Clinical recovery||129 (65)||106 (54)||0.17|
|Discharge||120 (60)||103 (52)||0.44|
|Death||16 (8)||21 (11)||0.70|
|Any adverse event (AE)||141 (71)||145 (74)||0.86|
|Grade ≥3 study drug-related AE||8 (4)||10 (5)||0.65|
|Study drug-related serious adverse event (SAE)||3 (2)||4 (2)||0.73|
|AE leading to discontinuation||9 (5)||20 (10)||0.07|
“These data are encouraging as they indicate that patients who received a shorter, 5-day course of remdesivir experienced similar clinical improvement as patients who received a 10-day treatment course,” said Aruna Subramanian, MD, Clinical Professor of Medicine, Chief, Immunocompromised Host Infectious Diseases, Stanford University School of Medicine, and one of the lead investigators of the study. “While additional data are still needed, these results help to bring a clearer understanding of how treatment with remdesivir may be optimized, if proven safe and effective.”