Label update is based on data from Phase IIIb DIALIZE trial
The Committee for Medicinal Products for Human Use (CHMP) of the European Medicines Agency (EMA) has adopted a positive opinion on a dosing and administration label update for AstraZeneca’s Lokelma (sodium zirconium cyclosilicate) to include patients with hyperkalaemia on stable haemodialysis.
The recommendation was based on data from the Phase IIIb DIALIZE trial, which showed a significant reduction in potassium levels pre-dialysis for patients receiving Lokelma, compared with placebo.1
Mene Pangalos, Executive Vice President, BioPharmaceuticals R&D, said: “Despite being on dialysis, many patients with renal disease still have high potassium levels, which can be life-threatening if left untreated. This recommendation underscores the clinical value that Lokelma could provide to physicians and patients who are looking to normalise potassium levels between dialysis sessions.”
In DIALIZE, 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 1.0% 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.1
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.
Hyperkalaemia is characterised by high levels of potassium in the blood, generally classified as greater than 5mmol/l.2 Many people living with chronic kidney disease (CKD) have hyperkalaemia despite being on haemodialysis and often experience fluctuations in their potassium levels.3,4 Patients with high variability in potassium levels between dialysis sessions are at significant risk of arrhythmias which can lead to cardiac arrest.3 Hyperkalaemia occurs in 23% to 47% of patients with CKD and/or heart failure with an estimated 700 million and 64 million people, respectively, living with each condition worldwide.5,6
DIALIZE is 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 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 full results of the DIALIZE trial were published in September 2019 in the Journal of the American Society of Nephrology.
Lokelma 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. It has been studied in three double-blinded, placebo-controlled trials and in one 12-month open label clinical trial in patients with hyperkalaemia.
AstraZeneca in CVRM
Cardiovascular, Renal and Metabolism (CVRM) together forms one of AstraZeneca’s three therapy 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 to protect organs and improve outcomes by slowing disease progression, reducing risks and tackling comorbidities. 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 cardiovascular health for millions of patients worldwide.
AstraZeneca (LSE/STO/NYSE: AZN) 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 and Metabolism, and Respiratory. 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.
1. Fishbane S et al. A Phase 3b, Randomized, Double-Blind, Placebo-Controlled Study of Sodium Zirconium Cyclosilicate for Reducing the Incidence of Predialysis Hyperkalemia. J Am Soc Nephrol 2019.
2. Kovesdy CP. Management of hyperkalaemia in chronic kidney disease. Nat Rev Nephrol. Nov 2014; 10:653-662.
3. Kovesdy CP. et al. Serum and Dialysate Potassium Concentrations and Survival in Hemodialysis Patients. Clin J Am Soc Nephrol. 2007:2:999-1007.
4. Evans KJ, Greenberg A. Hyperkalemia: A review. J Intensive Care Med. 2005;20:272-290.
5. 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.
6. James SL et al. Global, regional, and national incidence, prevalence, and years lived with disability for 354 diseases and injuries for 195 countries and territories, 1990–2017: A systematic analysis for the Global Burden of Disease Study 2017. The Lancet 2018; 392(10159):1789–858.