The European Commission (EC) has approved a dosing and administration label update in the EU for AstraZeneca’s Lokelma (sodium zirconium cyclosilicate) to include patients with hyperkalaemia on stable haemodialysis.
The approval by the EC was based on data from the Phase IIIb DIALIZE trial, the first ever randomised, placebo-controlled trial to evaluate a potassium binder in patients on stable haemodialysis.
The Phase IIIb, multicentre, double-blinded trial investigated the efficacy and safety of Lokelma versus placebo in 196 patients on haemodialysis with hyperkalaemia. Patients were randomised to receive Lokelma or placebo once daily on non-dialysis days for a treatment period of eight weeks. This included a four-week dose adjustment phase (starting at 5g and titrated weekly in 5g increments up to a maximum of 15g) and a four-week evaluation phase on stable dose.
The trial showed sustained potassium control pre-dialysis for more patients receiving Lokelma, compared with placebo. 41% of patients receiving Lokelma maintained pre-dialysis potassium levels on at least three out of four dialysis treatments after the long interdialytic interval and did not require urgent rescue therapy. This compared with 1% of patients receiving placebo, making it a statistically significant and clinically meaningful improvement. The safety profile of Lokelma observed in DIALIZE was consistent with previous trials.
Mene Pangalos, Executive Vice President, BioPharmaceuticals R&D, said: “More than 300,000 patients with end-stage renal disease in Europe are undergoing haemodialysis and are at risk of experiencing high potassium levels. This label update provides important guidance to manage hyperkalaemia, a condition which can be life-threatening in these patients if left untreated.”
Lokelma is a highly selective, oral potassium-removing agent currently approved in the US, EU, Canada, Hong Kong, China, Russia and Japan for the treatment of hyperkalaemia. Recently, the Food and Drug Administration (FDA) approved a label update in the US to include a dosing regimen specifically to treat hyperkalaemia in patients with end-stage renal disease on chronic haemodialysis.
The full results of the DIALIZE trial were published in September 2019 in the Journal of the American Society of Nephrology.