Green light from the European Medicines Agency for the use of remdesivir in Covid patients with severe kidney impairment, including those on dialysis. The green light for Gilead’s drug has arrived from the Committee for Medicinal Products for Human Use: now it will be up to the European Commission to examine the opinion of the CHMP. Should the recommendation be adopted, remdesivir would be the first authorized antiviral treatment against Sars-Cov2 that can be used in all phases of renal disease.
The incidence of the disease
In Europe, around 75 million people suffer from chronic kidney disease (CKD). Patients with advanced chronic kidney disease or end stage kidney disease (ESKD) constitute a population highly vulnerable to Covid-19: they are in fact at greater risk of mortality, with rates up to 21-25% and currently have of a limited number of safe and effective therapeutic options.
How remdesivir works
The clinical benefit of remdesivir in hospitalized COVID-19 populations is supported by randomized controlled trials, clinical practice evidence and meta-analyses, but previously its use in patients with severe renal impairment (<30 mL/min) was limited status, due to insufficient data. This positive opinion for use in people with severe renal impairment was based on results from a Phase I pharmacokinetic study (GS-US-540-9015), as well as results from the Phase III Redpine study, which evaluated the safety of remdesivir in hospitalized patients with Covid-19 and with severe renal impairment. No new safety signals were observed in either study.
“The Committee’s positive opinion helps validate the safety profile of remdesivir in people with severe renal impairment,” he announced. Tobias Welte, professor of pulmonary medicine and director of the department of pulmonary and infectious diseases at the Hanover University School of Medicine. “Expanding the use of remdesivir in this population, which still has limited treatment options, will help more people access treatment for COVID-19.”
In the European Economic Area (EEA), remdesivir is the only antiviral indicated for the treatment of Covid-19 both in adult and adolescent patients who do not require oxygen therapy and are at increased risk of developing a severe form of Covid-19, and in adults , adolescent, and pediatric patients with pneumonia requiring oxygen therapy (low- or high-flow oxygen or other noninvasive ventilation).
Gilead conducted a phase III, randomized, double-blind, parallel-group, placebo-controlled, multi-center study (Redpine) to evaluate the efficacy and safety of remdesivir in patients with severely reduced renal function hospitalized for Covid -19. The study enrolled 243 hospitalized adult participants with confirmed Covid-19 and renal impairment, who were randomized 2:1 to receive remdesivir (n=163) or placebo (n=80) in addition to standard of care, and were stratified for ESKD, high-flow oxygen demand and region (US vs. ex-US).
The study – which was terminated prematurely due to feasibility issues – was underpowered to evaluate efficacy, due to a smaller than expected enrollment. In the study, no new safety signals were observed and no additional adverse reactions to remdesivir were identified in 163 hospitalized patients with confirmed Covid-19 and acute kidney injury (Aki) (n=60), Ckd (eGFR < 30 mL/minute) (n=44) or Eskd (eGFR <15 mL/minute) requiring hemodialysis (n=59) who had received remdesivir for up to 5 days.
Pharmacokinetic data were obtained from the Redpine study – as well as an open-label, parallel group, single dose phase I study (GS-US-540-9015) –. Given the observed pharmacokinetics and the absence of new safety signals associated with increased metabolite levels in patients with severely reduced renal function, no dose adjustment of remdesivir is recommended in patients with renal impairment, including those on dialysis.
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