AstraZeneca has decided to discontinue the STABILIZE-CKD and DIALIZE-Outcomes phase III evidence trials for Lokelma (sodium zirconium cyclosilicate). The decision was made due to substantially increased enrolment timelines and low event rates, respectively, which made it prohibitive to deliver study results within a timeframe to meaningfully advance clinical practice.
STABILIZE-CKD and DIALIZE-Outcomes trials are part of the CRYSTALIZE evidence programme, which includes clinical and real-world evidence studies researching the potential benefit of Lokelma in the management of hyperkalaemia (HK) across the cardiorenal spectrum.
Sharon Barr, executive vice president, biopharmaceuticals R&D said: “Our ambitious CRYSTALIZE programme continues to generate evidence to improve the current management of hyperkalaemia, which we believe leads to better outcomes for cardiorenal patients when a potassium binder is included in their treatment regimen. Lokelma is the leading branded potassium binder globally and continues to benefit a broad hyperkalaemia patient population to achieve rapid, sustained potassium control and is well tolerated.”
The company will work with investigators to ensure the necessary follow-up with patients.
Lokelma is approved for the treatment of a broad HK patient population in 56 countries worldwide. The decision to discontinue the trials is not due to safety concerns and the positive benefit-risk of Lokelma does not change in the approved indication.
Hyperkalemia (HK) can be a chronic condition characterised by high levels of potassium in the blood, generally defined as greater than 5 mmol/L. Patients with high potassium levels are at significant risk of cardiac arrhythmias, which can lead to cardiac arrest. Worldwide there are about 840 million and 64 million people living with CKD and HF respectively, who are at an estimated two to three times higher risk of hyperkalemia. RAASi therapy is guideline-recommended to slow down CKD progression and reduce CV events, but the dose is often lowered or therapy is discontinued when HK is diagnosed. This has been shown to negatively impact patient outcomes, with mortality rates doubled for patients with CKD and HF whose RAASi had been down-titrated or discontinued compared to patients on maximum RAASi dose.
STABILIZE-CKD is a phase III randomised double-blind, placebo-controlled, multicentre study evaluating the effect of Lokelma, as an adjunct to optimised RAASi therapy (ACEi/ARB) on CKD progression in participants with CKD and HK or at-risk of HK. The study consists of a three-month up-titration period with an ACEi/ARB to guideline-recommended doses while taking Lokelma followed by a maintenance phase of two years with repeated estimated glomerular filtration rate (eGFR) measurements, originally planned to involve 1360 participants across the world.
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 HK. The study involves approximately 2,800 participants across the world.
Lokelma (sodium zirconium cyclosilicate) is an anti-hyperkalaemia (HK) therapy that provides rapid potassium reduction and sustained potassium control. It is indicated for the treatment of HK in adults, including patients with ESKD on chronic haemodialysis. It 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 and is odourless, tasteless, and stable at room temperature. Lokelma has been approved in more than 56 countries including US, EU, China and Japan.
Cardiovascular, renal and metabolism (CVRM), part of biopharmaceuticals, forms one of AstraZeneca’s main 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, liver and pancreas, AstraZeneca is investing in a portfolio of medicines for organ protection by slowing or stopping disease progression, and ultimately paving the way towards regenerative therapies. The company’s ambition is to improve and save the lives of millions of people, by better understanding the interconnections between CVRM diseases and targeting the mechanisms that drive them, so we can detect, diagnose and treat people earlier and more effectively.
AstraZeneca is a global, science-led biopharmaceutical company that focuses on the discovery, development, and commercialisation of prescription medicines in oncology, rare diseases, and biopharmaceuticals, including cardiovascular, renal & metabolism, and respiratory & immunology.
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