FDA Approves Lokelma for Hyperkalemia Treatment

Today the US Food and Drug Administration announced its approval of sodium zirconium cyclosilicate (Lokelma) for the treatment of hyperkalemia in adults.

A serious condition, hyperkalemia is characterized by elevated potassium levels often associated with cardiovascular, renal, and metabolic diseases. Lokelma, manufactured by AstraZeneca, is a highly-selective oral potassium-removing agent.

In March 2018, the European Commission (EC) granted AstraZeneca permission to market Lokelma in the European Union.

This approval would help address the life-threatening condition, said Elisabeth Björk, MD, PhD, vice president, head of cardiovascular, renal and metabolism, global medicines development at AstraZeneca.

“The consequences of hyperkalemia can be serious, even life-threatening, and can occur in patients either with chronic kidney disease or as a result of taking some medications for heart failure,” said Björk in a statement following the EC approval. “Today’s approval of Lokelma addresses a significant unmet need by bringing a rapid and sustained therapeutic option for patients with hyperkalemia.”

This approval drew on data from a 2-part, double-blind, randomized, placebo-controlled clinical trial (NCT01737697) in patients with hyperkalemia. The first phase included 753 patients with various conditions leading to hyperkalemia, including chronic kidney disease 60%, heart failure 10%, and diabetes mellitus 62%. Additionally, 67% were on renin angiotensin aldosterone system (RAAS) inhibitor therapy at baseline.

The study met its primary endpoint of a greater reduction in serum potassium levels for the 2.5g (-0.5; 95% CI; -0.5, -0.4), 5g (-0.5; 95% CI; -0.6, -0.5) and 10 g (-0.7; 95% CI; -0.8, -0.7) (3 times a day) dose groups compared to the placebo group (-0.2; 95% CI; -0.3, -0.2) P <0.001). during the initial 48 hours of study drug treatment.

In a subsequent 12-month, open-label trial, 99% of 751 hyperkalemic patients taking 10g of Lokelma 3 times a day achieved normokalemia (3.5-5.0 mEq/L) within 72 hours.

The initial recommended dose of Lokelma is 10 g administered 3 times a day for up to 48 hours. The recommended dose for ongoing treatment is 10 g once daily.

In placebo-controlled trials of the drug, edema was reported as an adverse event. In patients who were treated with Lokelma once per day edema was reported in 4.4% of patients receiving 5 g, 5.9% of patients receiving 10 g, and 16.1% of patients receiving 15 g, compared to 2.4% of patients receiving placebo.