Special Edition 2021

NEW PRODUCTS

remdesivir ( veklury °) and covid-19

Too many uncertainties over its efficacy as well as its harms

JUDGEMENT RESERVED The results of the main randomised placebo-­ controlled trial of remdesivir in adults hospi- talised for Sars-CoV-2 infection affecting their lungs (usually severely) showed no reduction in mortality, despite the inclusion of about 1000 patients. In this trial, remdesivir short- ened the “recovery” time in patients whose condition warranted supplemental oxygen or mechanical ventilation. Remdesivir can provoke hypersensitivity reactions and pos- sibly kidney and liver damage. The decision to authorise this product in July 2020, while so many uncertainties surrounded its harms and benefits, due to gaps in its evaluation, was very premature, if not reckless. Remde- sivir is still an experimental treatment; its evaluation in clinical trials should continue. VEKLURY° - remdesivir concentrate for solution for intravenous infusion, or powder for concentrate for solution for intravenous infusion • 100 mg of remdesivir per vial (both forms) ■ antiviral; adenosine nucleotide analogue ■ Indication : “ covid-19 in adults and adolescents (aged 12 years and older with body weight at least 40 kg) with pneumonia requiring supplemental oxygen ”. [EU centralised procedure]

Abstract

● The severity of covid-19, the disease caused by infection with the Sars-CoV-2 virus, varies greatly between patients. Most patients have a mild form that resolves without treatment. Other patients develop serious, and sometimes fatal, respiratory disorders and complications. ● Standard care as of mid-2020 mainly consists of treatments to relieve symptoms and other treatments to prevent certain complications. In a non-blinded randomised trial, 6 mg of dexa- methasone per day for up to 10 days, added to usual care, reduced mortality in patients receiv- ing invasive mechanical ventilation and, to a lesser degree, in those receiving oxygen . ● Remdesivir (Veklury°, Gilead Sciences) is a drug that disrupts the replication of viral RNA. It has been authorised in the European Union for use in adults and adolescents with covid-19 that is sufficiently severe to warrant supplemental oxygen . ● One double-blind placebo-controlled trial in 1062 adults hospitalised for covid-19 with pul- monary involvement found no statistically sig- nificant difference in mortality between the rem- desivir and placebo groups. ● In this trial, the median time to clinical improvement, mainly defined as the time to clinical discharge, was 10 days in the remdesivir group versus 15 days in the placebo group (p<0.001). Remdesivir had no effect on this end- point in patients with covid-19 considered mild or moderate. Remdesivir showed no efficacy in another double-blind placebo-controlled clin­ ical trial that included only 237 adults. ● The data concerning the drug’s adverse effects are extremely limited, leaving many questions unanswered. Remdesivir can provoke hyper- sensitivity reactions and possibly liver and kid- ney damage. ● As remdesivir is a substrate for various enzymes in vitro, many pharmacokinetic inter- actions are to be expected. Little is known about remdesivir’s potential effects on the metabolism of other drugs. No interaction studies have been conducted in humans.

©Prescrire ▶ Excerpt from Rev Prescrire November 2020 Volume 40 N° 445 • Pages 808-811

P age 6 • P rescrire I nternational S pecial E dition 2021