Lokelma granted Fast Track Designation in the US to reduce cardiovascular outcomes in patients on chronic haemodialysis with hyperkalaemia

AstraZeneca has been granted Fast Track Designation in the US for the investigation of Lokelma (sodium zirconium cyclosilicate) to reduce arrhythmia-related cardiovascular (CV) outcomes in patients on chronic haemodialysis with recurrent hyperkalaemia (HK). The designation is based on the potential of Lokelma to reduce serious adverse CV outcomes in this patient population, addressing a significant unmet medical need. This is being investigated in the ongoing Phase III DIALIZE-Outcomes trial.

HK is a prevalent condition in patients with chronic kidney disease (CKD) and heart failure (HF), affecting 24% to 48% of patients with moderate to advanced (stage 3-4) CKD and/or HF, and it remains a burden once patients are on chronic haemodialysis.1 In patients with end-stage renal disease (ESRD) receiving chronic haemodialysis, HK has been associated with an increased risk of all-cause and CV mortality, and hospitalisations.1,2

The Food and Drug Administration’s (FDA) Fast Track programme is designed to accelerate the development and review of new medicines for the treatment of serious conditions where there is an unmet treatment need.

Mene Pangalos, Executive Vice President, BioPharmaceuticals R&D, AstraZeneca said: “The DIALIZE-Outcomes trial is the first ever cardiovascular outcomes trial with a potassium binder in haemodialysis and has the potential to transform standard of care for these patients. The FDA decision demonstrates the importance of this trial, which will offer important information on Lokelma’s ability to reduce potentially deadly cardiovascular complications associated with hyperkalaemia for patients on chronic haemodialysis.”

The DIALIZE-Outcomes trial is part of the CRYSTALIZE evidence programme, which is comprised of over 50 clinical and real-world evidence studies researching the potential benefit of Lokelma in the management of HK across the cardiorenal spectrum. The DIALIZE-Outcomes trial is currently underway with results expected in 2024.

Lokelma is a highly selective, oral potassium-removing agent currently approved in the US, EU, Canada, Hong Kong, China, Russia, Japan and other countries for the treatment of HK. In 2020, the FDA and the European Commission (EC) approved label updates in the US and EU, respectively, to include a dosing regimen specifically to treat HK in patients with ESRD on chronic haemodialysis.


Hyperkalaemia is characterised by high levels of potassium in the blood, generally defined as greater than 5mmol/L.3 Many people living with chronic kidney disease (CKD) have hyperkalaemia despite being on haemodialysis and often experience fluctuations in their potassium levels 4,5 In Europe, approximately 300,000 patients with ESRD are undergoing haemodialysis, and more than 500,000 patients in the US are living with dialysis-dependent ESRD.6,7 Despite adequate haemodialysis, up to 25% of patients have serum potassium >5.5 mmol/L.8 Patients with high variability in potassium levels between dialysis sessions are at significant risk of arrhythmias, which can lead to cardiac arrest.4 Worldwide, there are an estimated 850 million and 64 million people living with CKD and HF respectively with hyperkalaemia occurring in an estimated 24% to 48% of patients with moderate to advanced (stage 3-4) CKD and/or HF.1,9,10

DIALIZE-Outcomes is a Phase III randomised, double-blind, placebo-controlled, multicentre study evaluating the effect of Lokelma on arrhythmia-related cardiovascular outcomes in patients on chronic haemodialysis with recurrent hyperkalaemia. The study consists of a 4-week dose-titration period followed by patient visits every 3 months over an average of 2 years. This is an international study involving approximately 300 sites across the US, Canada, Russia, Europe, Asia and South America.

Lokelma (sodium zirconium cyclosilicate) is an insoluble, non-absorbed sodium zirconium silicate, formulated as a powder for oral suspension, that acts as a highly selective potassium-removing medicine. It is administered orally, is odourless, tasteless and stable at room temperature.11,12 Lokelma is indicated for the treatment of hyperkalaemia in adults including patients on chronic haemodialysis.

AstraZeneca in CVRM
Cardiovascular, Renal and Metabolism (CVRM), part of BioPharmaceuticals, forms one of AstraZeneca’s three disease areas and is 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 for organ protection and improve outcomes by slowing disease progression, reducing risks and tackling co-morbidities. The Company’s 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 (LSE/STO/Nasdaq: AZN) is a global, science-led biopharmaceutical company that focuses on the discovery, development, and commercialisation of prescription medicines in Oncology, Rare Disease, and BioPharmaceuticals, including Cardiovascular, Renal & Metabolism, and Respiratory & Immunology. Based in Cambridge, UK, AstraZeneca operates in over 100 countries and its innovative medicines are used by millions of patients worldwide. Please visit astrazeneca.com and follow the Company on Twitter @AstraZeneca.

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2. Rosano GMC et al. Expert consensus document on the management of hyperkalaemia in patients with cardiovascular disease treated with renin angiotensin aldosterone system inhibitors: coordinated by the Working Group on Cardiovascular Pharmacotherapy of the European Society

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4. Kovesdy CP. et al. Serum and Dialysate Potassium Concentrations and Survival in Hemodialysis Patients. Clin J Am Soc Nephrol. 2007:2:999-1007.

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7. United States Renal Data System. 2018 Annual Data Report Volume 2: End-Stage Renal Disease Chapter 1: Incidence, Prevalence, Patient Characteristics, and Treatment Modalities. https://www.usrds.org/2018/view/v2_01.aspx. Published 2018. Accessed 1 May 2020.

8. Xu H, Ashfaq A, Karaboyas A, et al. Prevalence of hyperkalemia in DOPPS: a real-world, international cohort of hemodialysis patients. Nephrol. Dial. Transplant. 2017;32(3 Suppl):iii563

9. Jager KJ et al. A Single Number for Advocacy and Communication—Worldwide More than 850 Million Individuals Have Kidney Diseases. Nephrol Dial Transplant. 2019;34(11):1803-5.  

10. Vos T et al. Global, regional, and national incidence, prevalence, and years lived with disability for 328 diseases and injuries for 195 countries, 1990–2016: A systematic analysis for the Global Burden of Disease Study 2016. The Lancet 2017; 390(10100):1211–59.  

11. LOKELMA® (sodium zirconium cyclosilicate) US Prescribing Information; last update: Oct 2020 [cited 16 Nov 2021]. Available from: URL: https://www.azpicentral.com/lokelma/lokelma.pdf.

12. Kosiborod M et al. Effect of sodium zirconium cyclosilicate on potassium lowering for 28 days among outpatients with hyperkalemia: The HARMONIZE randomized clinical trial. JAMA 2014; 312(21):2223–33.

Veeva ID: Z4-40090
Date of Preparation: November 2021