Preliminary data reported for compassionate use of remdesivir

Experience with compassionate use of the intravenous antiviral agent remdesivir (Gilead Sciences) suggests it may have clinical benefit as a treatment for severe COVID-19, according to a group of international investigators who published their findings online (Grein J, et al. N Engl J Med. 2020 Apr 10 Epub ahead of print). https://www.ncbi.nlm.nih.gov/pubmed/32275812 The article presents efficacy and safety data from a series of 53 patients with confirmed SARS-CoV-2 infection and describes the outcomes as “the best currently available data” based on comparisons with contemporaneous cohorts from the literature. Patients were eligible to receive remdesivir if they had oxygen saturation ≤94% while breathing ambient air or were on oxygen support. They also had to agree not to be treated for COVID-19 with other investigational agents and meet criteria for hepatic enzymes. The 53 patients (ages 23 to 82 years) included 23 from North America (United States and Canada), 21 from Europe and nine from Japan. Median duration of symptoms before starting remdesivir was 12 days. Approximately two-thirds of patients were receiving invasive ventilation (median duration two days), and the same proportion had a medical comorbidity, with hypertension being the most common (25%). Remdesivir was given by infusion at a dose of 200mg on day 1 and 100mg on days 2 through 10. Four patients discontinued treatment prematurely because of adverse events. During median follow-up after starting remdesivir of 18 days, two-thirds of patients had improvement in oxygen support category and 25 patients (47%) were discharged. By Kaplan-Meier analysis, the 28-day cumulative incidence of clinical improvement (defined as a ≥2-point improvement on a six-point scale or hospital discharge) was 84%. Seven patients (13%) died. The mortality rate was 18% among patients receiving invasive ventilation and 5.3% among those receiving non-invasive oxygen support. Age ≥70 years and higher serum creatinine at baseline were also risk factors for mortality. Viral load data were not collected, precluding the ability to evaluate a viral suppressive effect of remdesivir or associations between change in viral load and patient outcomes. The safety analysis showed 32 patients (60%) reported adverse events, and 12 patients (23%) had serious adverse events. Hepatic enzyme elevation was the most common adverse event (23%) recorded. It was also noted in previous studies investigating remdesivir in healthy volunteers and patients with Ebola virus infection, but liver dysfunction is also common in patients with COVID-19. The authors described their experience as a preliminary report from a small cohort of patients. They noted that randomised, controlled trials investigating remdesivir are under way, including evaluation of a shorter duration of therapy.