FDA New Drug and Biologic Approvals, 2018 Midyear Review

Hyperkalemia: Lokelma (sodium zirconium cyclosilicate)

Indication: Indicated for nonemergent treatment of hyperkalemia in adults.

Dosage:

Initial: 10 g PO TID for up to 48 hr.

Maintenance: Range is from 5 g every other day to 15 g/day depending on target potassium level.

Mechanism: Potassium binder. Nonabsorbed zirconium silicate preferentially captures potassium in exchange for hydrogen and sodium. Fecal potassium excretion is increase by binding of potassium in the lumen of the GI tract. Potassium binding reduces the free potassium concentration in the GI lumen, thereby lowering serum potassium level.

Approval was based on the HARMONIZE clinical trial, which compared zirconium cyclosilicate with placebo in outpatients with hyperkalemia (serum potassium levels 5.1 mEq/L or higher). In the open-label phase, serum potassium levels declined from 5.6 mEq/L at baseline to 4.5 mEq/L at 48 hours. Median time to normalization was 2.2 hours, with 84% of patients achieving normokalemia by 24 hours and 98% by 48 hours. In the randomized phase, serum potassium was significantly lower during days 8-29 with all 3 zirconium cyclosilicate doses vs placebo (4.8 mEq/L, 4.5 mEq/L, and 4.4 mEq/L for 5 g, 10 g, and 15 g; 5.1 mEq/L for placebo; P <0.001 for all comparisons).

The HARMONIZE trial also looked at patients with heart failure who were maintained on renin-angiotensin-aldosterone system inhibitors (RAASi), which are known to cause elevated serum potassium levels. Compared with placebo, all 3 zirconium cyclosilicate doses lowered potassium and effectively maintained normokalemia for 28 days in patients with heart failure without adjusting concomitant RAASi.

References:

• Kosiborod M, Rasmussen HS, Lavin P, et al. Effect of sodium zirconium cyclosilicate on potassium lowering for 28 days among outpatients with hyperkalemia: the HARMONIZE randomized clinical trial. JAMA. 2014 Dec 3;312(21):2223-33. https://www.ncbi.nlm.nih.gov/pubmed/25402495

• Anker SD, Kosiborod M, Zannad F, et al. Maintenance of serum potassium with sodium zirconium cyclosilicate (ZS-9) in heart failure patients: results from a phase 3 randomized, double-blind, placebo-controlled trial. Eur J Heart Fail. 2015 Oct;17(10):1050-6. https://www.ncbi.nlm.nih.gov/pubmed/26011677

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Cite this: Mary L Windle. FDA New Drug and Biologic Approvals, 2018 Midyear Review - Medscape - Aug 01, 2018.