Topline results from an open-label phase III trial of the novel antiviral remdesivir in hospitalized Covid-19 patients demonstrated efficacy for both 10-day and 5-day dosing, with no new safety signals, according to Gilead Sciences.
In a separate release, the company said that it is aware that a National Institute of Allergy and Infectious’ Diseases trial of remdesivir “has met its primary endpoint and that NIAID will provide detailed information at an upcoming briefing.”
At the same time, the Lancet published the results of a randomized, placebo-controlled trial of remdesivir from Wuhan that suggests the antiviral did not speed recovery or reduce deaths, although they did find some benefit in clinical improvement and shorter periods on mechanical ventilation compared to placebo. However, it must be noted that this study was stopped early because of the difficulty of recruiting patients after the outbreak in Wuhan, and the study authors noted that more research is needed.
In the study from Gilead Sciences, 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,” the company said in a prepared statement. “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.
“Outside of Italy, the overall mortality rate at Day 14 was 7 percent (n=23/320) across both treatment groups, with 64 percent (n=205/320) of patients experiencing clinical improvement at Day 14 and 61 percent (n=196/320) of patients discharged from the hospital,” the company reported.
Results of an exploratory analysis, also released by the company, suggested that patients who were treated within 10 days of symptom onset fared better.
“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.”
But, the efficacy outcome measure was an increase of 2 or more points on an ordinal scale, and while 129 of 200 patients in the 5-day treatment arm and 107 of the 197 patient in the 10-day treatment group achieved that mark, the adjusted P value was 0.16. Likewise, values for clinical recovery, discharge, and death were 0.17, 0.44, and 0.70, respectively.
The most common adverse events were “nausea (5-day: 10.0%, n=20/200 vs 10-day: 8.6%, n=17/197) and acute respiratory failure (5-day: 6.0%, n=12/200 vs 10-day: 10.7%, n= 21/197). Grade 3 or higher liver enzyme (ALT) elevations occurred in 7.3 percent (n=28/385) of patients, with 3.0 percent (n=12/397) of patients discontinuing remdesivir treatment due to elevated liver tests.”
The results reported by Gilead come from one of two open-label phase 3 trials (SIMPLE). “The initial phase of the study randomized 397 patients in a 1:1 ratio to receive remdesivir 200 mg on the first day, followed by remdesivir 100 mg each day until day 5 or 10, administered intravenously, in addition to standard of care. An expansion phase of the study was recently added and will enroll an additional 5,600 patients, including patients on mechanical ventilation,” the company reported. “The study is being conducted at 180 trial sites around the world, including sites in the United States, China, France, Germany, Hong Kong, Italy, Japan, Korea, the Netherlands, Singapore, Spain, Sweden, Switzerland, Taiwan and the United Kingdom.
“A second SIMPLE trial is evaluating the safety and efficacy of 5-day and 10-day dosing durations of remdesivir administered intravenously in patients with moderate manifestations of COVID-19, compared with standard of care. The results from the first 600 patients of this study are expected at the end of May.”
Peggy Peck, Editor-in-Chief, BreakingMED™
Cat ID: 125
Topic ID: 79,125,730,933,125,190,520,926,192,927,151,928,195,929,925,934
