In Phase IIIb DIALIZE trial, 41.2% of Lokelma patients maintained normal potassium levels pre-dialysis compared to 1% receiving placebo
AstraZeneca today 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.1,2,3,4 Many patients with ESRD have hyperkalaemia despite being on haemodialysis.5,6 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.
The risk of hyperkalaemia is associated with common comorbidities including chronic kidney disease (CKD), heart failure (HF) and diabetes, and these are the same conditions in which renin-angiotensin-aldosterone system (RAAS) inhibitors are recommended in guidelines. To help prevent the recurrence of hyperkalaemia, important guideline-recommended RAAS inhibitor therapy is often modified or discontinued.Hyperkalaemia occurs in 23% to 47% of patients with CKD and/or HF, with an estimated 200 million and 64 million people, respectively, living with each condition worldwide.
DIALIZE is the first ever randomised, placebo-controlled trial to evaluate a potassium binder in patients on stable haemodialysis. The Phase IIIb, multicentre, double-blind trial investigated the efficacy 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 8 weeks. This included a 4 week dose adjustment phase (starting at 5 g and titrated weekly in 5 g increments up to a maximum of 15 g) and a 4 week evaluation phase on stable dose.
Lokelma is an insoluble, non-absorbed sodium zirconium silicate, formulated as a powder for oral suspension, that acts as a highly-selective potassium-removing agent. It is administered orally, is odourless, tasteless and stable at room temperature. It has been studied in three double-blinded, placebo-controlled trials and in one 12-month open label clinical trial in patients with hyperkalaemia.
About AstraZeneca in CV, Renal & Metabolism (CVRM)
CV, renal and metabolism together form one of AstraZeneca’s main therapy areas and a key growth driver for the Company. By following the science to understand more clearly the underlying links between the heart, kidneys and pancreas, AstraZeneca is investing in a portfolio of medicines to protect organs and improve outcomes by slowing disease progression, reducing risks and tackling co-morbidities. Our ambition is to modify or halt the natural course of CVRM diseases and potentially regenerate organs and restore function, by continuing to deliver transformative science that improves treatment practices and CV health for millions of patients worldwide.
AstraZeneca is a global, science-led biopharmaceutical company that focuses on the discovery, development and commercialisation of prescription medicines, primarily for the treatment of diseases in three therapy areas - Oncology, Cardiovascular, Renal & Metabolism and Respiratory. AstraZeneca operates in over 100 countries and its innovative medicines are used by millions of patients worldwide.For more information, please visit astrazeneca.comand follow us on Twitter @AstraZeneca.
|Gonzalo Viña||+44 203 749 5916|
|Rob Skelding||Oncology||+44 203 749 5821|
|Rebecca Einhorn||Oncology||+1 301 518 4122|
|Matt Kent||BioPharma||+44 203 749 5906|
|Jennifer Hursit||Other||+44 203 749 5762|
|Christina Malmberg Hägerstrand||Sweden||+46 8 552 53 106|
|Michele Meixell||US||+1 302 885 2677|
|Thomas Kudsk Larsen||+44 203 749 5712|
|Henry Wheeler||Oncology||+44 203 749 5797|
|Christer Gruvris||BioPharma (cardiovascular; metabolism)||+44 203 749 5711|
|Nick Stone||BioPharma (respiratory; renal)||+44 203 749 5716|
|Josie Afolabi||Other||+44 203 749 5631|
|Craig Marks||Finance; Fixed Income||+44 7881 615 764|
|Jennifer Kretzmann||Retail Investors; Corporate Access||+44 203 749 5824|
|US toll-free||+1 866 381 72 77|
1. Kosiborod M, Rasmussen HS, Lavin P, et al. ‘Effect of Sodium Zirconium Cyclosilicate on Potassium Lowering for 28 Days Among Outpatients With Hyperkalemia.’ JAMA. 2014. doi:10.1001/jama.2014.15688.
2. Packham D, Rasmussen HS, Lavin P, et al. ‘Sodium Zirconium Cyclosilicate in Hyperkalemia.’ New Engl J Med. 2015; 372:222-31. doi:10.1056/NEJMoa1411487.
3. Ash S, Bhupinder S, Lavin P, et al. ‘A phase 2 study on the treatment of hyperkalemia in
patients with chronic kidney disease suggests that the selective potassium trap, ZS-9, is safe and efficient.’ Kidney Int. 2015; 88:404-411. doi:10.1038/ki.2014.382.
4. National Kidney Foundation. ‘Clinical Update on Hyperkalemia." 2014. Accessed 5 January 2017.
5. Csaba P et al. Serum and Dialysate Potassium Concentrations and Survival in Hemodialysis Patients. Clin J Am Soc Nephrol. 2007:2: 999-1007.
6. Evans KJ, Greenberg A. Hyperkalemia: A review. J Intensive Care Med. 2005;20:272-290.
AstraZeneca är ett globalt, innovationsdrivet bioläkemedelsföretag med fokus på forskning, utveckling och marknadsföring av receptbelagda läkemedel, primärt för behandling av sjukdomar inom tre huvudsakliga terapiområden: cancer, kardiovaskulära sjukdomar, njursjukdomar och metabola sjukdomar och sjukdomar i andningsvägarna. Bolaget är också selektivt aktivt inom autoimmunitet, neurovetenskap och infektion. AstraZeneca bedriver verksamhet i över 100 länder och dess innovativa läkemedel används av miljontals patienter över hela världen.