Phase IIIb DIALIZE trial resultsof Lokelma for hyperkalaemia in patients with end-stage renal disease on haemodialysis

AstraZeneca presented positive results from the Phase IIIb DIALIZE trial which investigated the efficacy and safety of Lokelma (sodium zirconium cyclosilicate) for the treatment of hyperkalaemia in patients with end-stage renal disease (ESRD) on haemodialysis. Hyperkalaemia is a serious condition characterised by elevated potassium levels in the blood.

In the trial, 41.2% of patients with hyperkalaemia on stable haemodialysis receiving Lokelma maintained pre-dialysis normal potassium levels (4-5 mmol/L) on at least three out of four dialysis treatments after the long interdialytic interval and did not require urgent rescue therapy, compared to 1.0% of patients receiving placebo. This was a statistically significant and clinically meaningful improvement. The safety profile of Lokelma observed in DIALIZE was consistent with previous trials. The results were presented as a late-breaking abstract at the 56th European Renal Association – European Dialysis and Transplant Association (ERA-EDTA) Congress in Budapest, Hungary and were published in the Journal of the American Society of Nephrology.

Elisabeth Björk, Senior Vice President, Head of Late-stage Development, Cardiovascular, Renal and Metabolism, BioPharmaceuticals R&D, said: “These positive results show that Lokelma can normalize potassium levels in between dialysis sessions for patients with hyperkalaemia who have end-stage renal disease. There is a high unmet treatment need that affects a large patient population and we believe Lokelma can play a critical role.”

Steven Fishbane, MD, Zucker School of Medicine at Hofstra/Northwell, Great Neck, NY, and primary investigator in the DIALIZE trial, said: “An estimated two million people worldwide have end-stage renal disease, placing them at a higher risk for hyperkalaemia. Despite being on dialysis, many still have high potassium levels, which can be life-threatening if left untreated. These results provide important insights for the clinical community and patients, and have the potential to transform the treatment paradigm.”

Hyperkalaemia can be a result of cardiovascular, renal and metabolic diseases, and use of certain medications such as renin-angiotensin-aldosterone system (RAAS) inhibitors. Many patients with ESRD have hyperkalaemia despite being on haemodialysis. Prevalence and severity of hyperkalaemia is highest after the long interdialytic interval, the longest number of days between dialysis sessions. Lokelma is a highly-selective, oral potassium-removing agent currently approved and available in the US and EU for the treatment of adults with hyperkalaemia. Data from the DIALIZE trial will support label updates in the US and EU as the dosing regimen used in the trial is not currently approved.

See- "A Phase IIIb, Randomized, Double-Blind, Placebo-Controlled Study of Sodium Zirconium Cyclosilicate for Reducing the Incidence of Predialysis Hyperkalemia" JASN June 2019, ASN.2019050450; DOI: https://doi.org/10.1681/ASN.2019050450.