AZ drops two trials aimed at expanding Lokelma’s label

AstraZeneca has decided to abandon two phase 3 trials of its drug to reduce high levels of potassium in the blood (hyperkalaemia) – Lokelma – in patients with kidney disease.

The STABILIZE-CKD and DIALIZE-Outcomes studies – part of AZ’s CRYSTALIZE programme for the drug – have been shelved because patients were being enrolled into them more slowly than hoped for, and clinical events were occurring at a lower rate than expected.

As a result, it has become “prohibitive to deliver study results within a timeframe to meaningfully advance clinical practice,” said AZ in a statement.

Lokelma (sodium zirconium cyclosilicate) – formerly known as ZS9 – has been approved since 2018 as a treatment for hyperkalaemia after nearly two years of delay caused by problems at the drug’s manufacturing facilities.

The risk of hyperkalemia increases significantly for patients with chronic kidney disease (CKD) and for those who take common medications for heart failure (HF), such as renin-angiotensin-aldosterone system (RAAS) inhibitors, which can increase potassium in the blood.

Since the approval, AZ has been running studies trying to build the dataset for Lokelma and encourage the use of the drug, which was predicted to have blockbuster potential at launch. It hasn’t met those lofty expectations, but has started to build momentum, with sales up 49% to $300 million in the first nine months of this year.

STABILIZE-CKD is a phase 3 study looking at Lokelma as an adjunct to optimised RAAS therapy on CKD progression in participants with CKD who either already have hyperkalaemia or are at risk of developing the condition. It was originally intended to enrol 1,360 patients who would be followed up over a two-year period with measurements of their kidney function.

DIALIZE-Outcomes, meanwhile, is a phase 3 study evaluating the effect of Lokelma on arrhythmia-related cardiovascular outcomes in patients on chronic haemodialysis with recurrent hyperkalaemia, with a target population of 2,800 subjects.

Both of the trials started in 2021, while the COVID-19 pandemic was still in full swing, and were expected to support regulatory filings from late-2024 onwards.

“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,” said Sharon Barr, head of biopharma R&D at AZ.

“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,” she added.

The UK pharma added Lokelma to its pipeline through its $2.7 billion acquisition of ZS Pharma in 2015. It competes in the market with CSL Vifor’s Veltassa (patiromer), whose annual sales are currently running at a little over $110 million, but is considered to have a faster onset of action.