Although controlled trial results of remdesivir for COVID-19 won't be available for several weeks, early experience with compassionate use is detailed in a new NEJM report.
Remdesivir could benefit some patients with severe coronavirus disease 2019 (COVID-19) according to early experience from its off-label, compassionate-use program. This is according to a new report published in NEJM, which may only be weeks ahead of more controlled trial results.
"Although data from several ongoing randomized, controlled trials will soon provide more informative evidence regarding the safety and efficacy of remdesivir for COVID-19, the outcomes observed in this compassionate-use program are the best currently available data," advised lead author John Grein, MD, Cedars-Sinai Medical Center and colleagues.
"We are still on track to provide data for remdesivir in the coming weeks," Chris Ridley, senior director, media relations for Gilead Sciences, told Contagion® on March 31st.
The report from the compassionate-use program was based on data that were available for 53 of the first 61 patients receiving at least 1 dose of remdesivir to treat COVID-19. The patients were hospitalized in the United States, Europe, Canada or Japan with COVID-19 diagnosis confirmed by SARS-CoV-2 reverse-transcriptase-polymerase-chain reaction assay. Each patient had oxygen saturation of 94% or less on ambient air or was receiving oxygen support; and was eligible to receive the drug if creatinine clearance was above 30ml/minute and serum level of alanine aminotransferase (ALT) was less than 5 times the upper limit of normal range.
The remdesivir regimen consisted of a loading dose of 200mg intravenously on day 1 followed by 100mg daily for 9 days. Due to either improvement allowing hospital discharge, adverse drug effect, or deterioration and fatality, 3 patients received fewer than 5 days; 10 received 5 to 9 days of treatment; and 40 of the 53 patients received the full 10-day course. Supportive treatment was at the clinician's discretion and could vary between patients and sites of care.
During a median follow-up of 18 days, 36 patients (68%) had lessened need for oxygen support, including 17 of 30 patients (57%) who had required mechanical ventilation and were able to be extubated. Improvement from less oxygen requirement was observed in the 12 patients who were breathing ambient air or low-flow supplemental oxygen and in 5 of the 7 patients receiving noninvasive oxygen support as positive pressure or high-flow supplemental oxygen.
Mortality was 18% (6 of 34 patients) among the patients receiving invasive ventilation and 5% (1 of 19) among those without that requirement. Twenty-five of the 53 patients (47%) were able to be discharged from the hospital.
Serious adverse events were reported in 12 patients (23%), each of whom was on invasive ventilation at baseline. The remdesivir had to be discontinued in 4 patients due to either worsening of preexisting renal failure (1); multiple organ failure (1); or elevated aminotransferases (2), with 1 of these patients also exhibiting maculopapular rash.
In absence of a control group comparator, the investigators offered comparison of their findings with published studies, including a recent controlled trial of lopinavir-ritonavir associated with a 28-day mortality of 22%; and case series and cohort studies from China with mortality rates ranging between 17 to 78%.
Although acknowledging the differences between studied populations and conditions, Grein and colleagues claimed, "by way of comparison, the 13% mortality observed in this remdesivir compassionate-use cohort is noteworthy, considering the severity of disease in this patient population."
In an open letter on March 28th, Daniel O'Day, chief executive officer of Gilead, announced the expansion of the compassionate-use program, from the traditional requirement of single applicants to an "expanded access" that will allow for an application to cover multiple severely ill patients.
"Remdesivir is still an investigational medicine, " O'Day cautioned. "We are planning for the outcome we all hope for—that it will prove to be a safe, effective treatment—and in the meantime we are taking the ethical, responsible approach to determining whether that is the case."