AstraZeneca calls it quits on pair of trials for hyperkalemia drug it scored in buyout of ZS Pharma

After a hard-fought battle for FDA approval, AstraZeneca has hit another setback on its quest to turn its potassium-reduction drug Lokelma into a blockbuster.

AstraZeneca has put the kibosh on two late-stage Lokelma trials testing the hyperkalemia drug in patients with heart and kidney diseases. The studies, dubbed STABILIZE-CKD and DIALIZE-Outcomes, were called off due to “substantially increased enrollment times and low event rates,” respectively, AZ said in a press release Friday.

Those hurdles made it “prohibitive” for the trials to read out within the timeframe required to meaningfully advance clinical practice, AstraZeneca added.

Hyperkalemia is the term for elevated levels of potassium in the blood. Patients with higher potassium levels are at risk of cardiac arrhythmias, which can lead to cardiac arrest, AZ explained. Globally, there are about 840 million patients with chronic kidney disease (CKD) and 64 million with heart failure, many of whom will develop hyperkalemia.

Those patients often receive renin–angiotensin–aldosterone system inhibitor (RAASi) drugs to slow down CKD progression and reduce cardiovascular events. But the dose is often lowered or therapy is discontinued when hyperkalemia is diagnosed, leading to worse patient outcomes, AZ said.

As for the trials themselves, STABILIZE-CKD was testing the effects of Lokelma and optimized RAASi therapy on CKD progression in kidney disease patients either with or at-risk of hyperkalemia. DIALIZE-Outcomes, for its part, evaluated the effects of Lokelma alone on arrhythmia-related cardiovascular outcomes in patients on chronic hemodialysis with recurrent hyperkalemia.

The move to discontinue the studies isn’t influenced by safety concerns and the positive benefit-risk profile of Lokelma remains intact in its approved indication, AstraZeneca said in its release. In 2018, after several years of rejections spurred by manufacturing problems, the drug won an approval to treat hyperkalemia in adults.

The drug, which formerly went by the code name ZS-9, was one of the motivations behind AstraZeneca’s $2.7 billion buyout of ZS Pharma back in 2015. At the time, the companies hoped they could turn Lokelma into a blockbuster.

AZ’s hyperkalemia drug still has a long way to go before it breaks the billion-dollar threshold, however. In 2022, the medication brought home global sales of $289 million.

Meanwhile, analysts at GlobalData earlier this month predicted Lokelma could generate around $799 million in 2029.