Label update is based on data from Phase IIIb DIALIZE trial
Today, the US Food and Drug Administration (FDA) approved a label update in the US for AstraZeneca’s Lokelma (sodium zirconium cyclosilicate) to include a dosing regimen specifically to treat hyperkalaemia in patients with end-stage renal disease on chronic haemodialysis.
The approval by the US FDA was based on positive results from the Phase IIIb DIALIZE trial, the first ever randomised, placebo-controlled trial to evaluate a potassium binder in patients on stable haemodialysis.1 The DIALIZE trial showed that a significantly higher proportion of patients in the Lokelma group (41.2%) met the primary endpoint and were classified as responders (maintained serum potassium 4-5 mmol/L during at least three out of four haemodialysis sessions after the long interdialytic interval [LIDI] of the last four weeks of treatment and did not require urgent rescue therapy) compared to patients in the placebo group (1.0%), making it a statistically significant (P<0.001) and clinically meaningful improvement.1 Rescue therapy was defined as any urgent therapeutic intervention considered necessary to reduce serum potassium for severe hyperkalaemia (serum potassium >6.0 mmol/L). The safety profile of Lokelma observed in DIALIZE was consistent with previous trials.1
Lokelma is a potassium binder indicated for the treatment of hyperkalaemia in adults.2 Lokelma should not be used as an emergency treatment for life-threatening hyperkalaemia because of its delayed onset of action.2 This is the first label update for Lokelma in the US following its FDA approval in 2018 to treat adults with hyperkalaemia. The label update now includes a dosing regimen for patients on chronic haemodialysis with a starting dose of 5 g once daily on non-dialysis days and a starting dose of 10 g once daily on non-dialysis days in patients with serum potassium greater than 6.5 mmol/L.
Mene Pangalos, Executive Vice President, BioPharmaceuticals R&D, said: “More than 500,000 patients in the US are living with dialysis-dependent end-stage renal disease and could be at risk for dangerously high levels of potassium. With this FDA approved update, the Lokelma label now includes important dosing guidance for treating hyperkalaemia in patients on haemodialysis.”
Lokelma is currently approved in the US, EU, Canada, China, Russia and Japan for the treatment of patients with hyperkalaemia. Lokelma recently received a positive opinion from The Committee for Medicinal Products for Human Use (CHMP) of the European Medicines Agency (EMA) on a dosing and administration label update to include patients with hyperkalaemia on stable haemodialysis. A final decision is expected from the European Commission in the near-future.
Hyperkalaemia is characterised by high levels of potassium in the blood, generally classified as greater than 5 mmol/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 Patients with high variability in potassium levels between dialysis sessions are at significant risk of arrhythmias which can lead to cardiac arrest.4 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.6-8
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 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 (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. It has been studied in three double-blinded, placebo-controlled trials, in one 11-month open label clinical trial 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 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 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. LOKELMA® (sodium zirconium cyclosilicate) [prescribing information]. Wilmington, DE: AstraZeneca Pharmaceuticals LP; 2018. Accessed March 25, 2020.
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7. 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.
8. 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.