Lokelma launches in Korea…targeting the gap in hyperkalemia management

First new drug in over 40 years… Expectations rise for a shift in RAAS inhibitor maintenance strategy

Potassium reduction within 1 hour—88% maintained for 12 months… secures clinical evidence

A new drug capable of resolving the treatment dilemma of discontinuing RAAS inhibitors during hyperkalemia management has been introduced in Korea.

The new potassium binder ‘Lokelma,’ supported by clinical evidence, is being presented as an option to support a strategy of maintaining RAAS inhibitors, raising the possibility of a shift in the treatment paradigm.

On the 22nd, AstraZeneca Korea held a press conference at the Plaza Hotel in Jung-gu, Seoul to mark the domestic launch of Lokelma (sodium zirconium cyclosilicate, SZC), a treatment for adult hyperkalemia.

Lokelma is a new drug approved by the Ministry of Food and Drug Safety last November, and represents the first new treatment option in the hyperkalemia field in Korea introduced in about 40 years. Unlike existing organic polymer-based adsorbents, it is an inorganic crystalline potassium binder that selectively captures potassium throughout the gastrointestinal tract and excretes it from the body. In vitro studies confirmed that its potassium selectivity is more than 125 times higher than that of existing treatments, and its non-absorbable nature is also cited as a key differentiator.

Hyperkalemia is defined as a serum potassium level exceeding 5.0 mmol/L and commonly occurs in patients with chronic kidney disease, heart failure, and diabetes. In particular, it occurs in 40–50% of patients with chronic kidney disease, and it is reported that approximately one in three (32.8%) patients taking RAAS inhibitors experience hyperkalemia at least once. If it progresses to a severe stage, it can lead to fatal outcomes such as arrhythmia and cardiac arrest.

Bum Soon Choi, Professor of Nephrology at Eunpyeong St. Mary’s Hospital

The problem lies in conflicting treatment strategies. While RAAS inhibitors are key medications for protecting the heart and kidneys, their tendency to elevate potassium levels often leads to dose reduction or discontinuation when hyperkalemia occurs.

Bum Soon Choi, Professor of Nephrology at Eunpyeong St. Mary’s Hospital, said, “Hyperkalemia is highly recurrent and must be managed as a chronic condition. However, reducing or discontinuing RAAS inhibitors for this reason can worsen the prognosis of cardiac and renal diseases. Since guidelines also recommend maintaining RAAS inhibitors whenever possible, we need treatment strategies that support this.”

In fact, guidelines including those from KDIGO and the Korean Society of Nephrology also mention the use of potassium binders as an adjunct strategy to maintain RAAS inhibitor therapy.

The presentation highlighted data on the clinical efficacy and treatment persistence of Lokelma.

Professor Kim Se-jung of Nephrology at Seoul National University Bundang Hospital evaluated, “Lokelma has demonstrated potassium reduction within one hour of administration, long-term maintenance of potassium control, continuation of RAAS inhibitor therapy, and good tolerability.”

Sejoong Kim, Professor of Nephrology, Seoul National University Bundang Hospital

In the Phase 3 ZS-003 study, 753 patients with hyperkalemia were administered 10 g of Lokelma. The results showed a significant decrease in serum potassium levels within one hour, and the proportion of patients reaching normal ranges within 48 hours was 86.4%, which was higher than the 47.8% observed in the placebo group.

Furthermore, in the HARMONIZE (ZS-004) study, the mean serum potassium level decreased from 5.6 mmol/L to 4.5 mmol/L within 48 hours, and patients maintained stable, low potassium levels during the maintenance phase.

The efficacy was also sustained in long-term data. In the ZS-005 study, 88% of patients maintained normal potassium levels after up to 12 months of treatment, and 87% of patients previously using RAAS inhibitors were able to continue or increase their treatment.

In terms of tolerability, an overall favorable safety profile was confirmed in clinical trials involving approximately 1,760 non-dialysis hyperkalemia patients. The most common adverse event, edema, was mostly mild to moderate, and gastrointestinal symptoms such as constipation were manageable through dose adjustment or discontinuation.

Professor Choi stated, “Existing chelate-based potassium binders had limitations such as slow onset of action and low compliance due to inconvenience in administration. There has been a continuous demand in clinical practice for new options that allow sustained treatment.”

Professor Sejoong Kim emphasized, “Locelma is a treatment option that can help patients maintain RAAS inhibitor therapy without discontinuation when hyperkalemia occurs. Based on clinical evidence, it will serve as a meaningful alternative capable of changing treatment strategies in actual clinical practice.”