AstraZeneca's Lokelma (Sodium Zirconium Cyclosilicate) Receives FDA Label Update with Dosing Guidance for Hyperkalemia in End-Stage Renal Disease Patients on Hemodialysis

April 28, 2020 /Bio ValleyBIOON/ ---AstraZeneca(AstraZeneca) recently announced that the U.S. Food and Drug Administration (FDA) has approved the label update for its novel oral potassium-lowering drug Lokelma® (Lokelma®, generic name: sodium zirconium cyclosilicate), incorporating a dosing regimen specifically indicated for the treatment of hyperkalemia in patients with end-stage renal disease (ESRD) receiving chronic dialysis.

This approval is based on the positive results from the Phase IIIb DIALIZE trial, the first randomized, placebo-controlled trial ever conducted to evaluate a potassium binder in patients on stable dialysis. The trial assessed the efficacy and safety of Lokelma for the treatment of hyperkalemia in patients with end-stage renal disease (ESRD) receiving stable dialysis.

The results showed that a significantly higher proportion of patients (41.2%) in the Lokelma treatment group achieved the primary endpoint and were classified as responders (maintaining normal pre-dialysis potassium levels [4-5 mmol/L] during three-quarters of hemodialysis sessions following the long interdialytic interval [LIDI] in the last 4 weeks of treatment, without requiring emergency rescue therapy), compared to only 1.0% in the placebo group. The data were statistically significant (p < 0.001) and clinically meaningful. Rescue therapy refers to any necessary emergency therapeutic intervention for severe hyperkalemia to lower serum potassium levels. The safety profile of Lokelma observed in this trial was consistent with previous trials.

Lokelma is a potassium binder indicated for the treatment of hyperkalemia in adults. Due to its delayed onset of action, Lokelma should not be used as an emergency treatment for life-threatening hyperkalemia.

This approval follows the 2018FDAFirst U.S. Label Update for Lokelma Following Approval for the Treatment of Hyperkalemia in Adults. The updated label now includes a dosing regimen for patients on chronic hemodialysis: an initial dose of 5 g once daily on non-dialysis days; and an initial dose of 10 g once daily on non-dialysis days for patients with serum potassium >6.5 mmol/L.

Mene Pangalos, Executive Vice President of AstraZeneca’s Biopharmaceuticals R&D, stated: “More than 500,000 patients in the United States have dialysis-dependent end-stage renal disease and may be at risk of hyperkalemia. WithFDAApproved Update: The Lokelma Label Now Includes Important Dosing Guidelines for the Treatment of Hyperkalemia in Patients Undergoing Hemodialysis.

Hyperkalemia (typically classified as serum potassium levels >5.0 mmol/L) is a serious condition characterized by elevated potassium levels in the blood, with a high prevalence among patients with chronic kidney disease (CKD) and/or heart failure (HF). Patients undergoing hemodialysis or those using conventional cardiac medications (such as renin-angiotensin-aldosterone system inhibitors) are at even higher risk of developing hyperkalemia. Globally, there are up to 700 million patients with CKD and up to 64 million patients with HF. Among patients with CKD and/or HF, the incidence of hyperkalemia ranges from 23% to 47%.

The active pharmaceutical ingredient of Lokelma is sodium zirconium cyclosilicate, a water-insoluble, non-absorbed potassium binder indicated for the treatment of hyperkalemia in adults. Sodium zirconium cyclosilicate employs an innovative ion-trapping technology with high selectivity for potassium ions, thereby offering a faster onset of action and better tolerability. Regardless of the underlying cause of hyperkalemia, and irrespective of age, sex, race, presence of comorbidities, or concurrent use of renin-angiotensin-aldosterone system inhibitors (RAASi), sodium zirconium cyclosilicate can reduce serum potassium levels and maintain them within the normal range.

To date, Lokelma has been approved in the United States, the European Union, Canada, China (including mainland China and Hong Kong), Russia, and Japan for the treatment of patients with hyperkalemia. Recently, Lokelma received a positive opinion from the Committee for Medicinal Products for Human Use (CHMP) of the European Medicines Agency (EMA) regarding the update of its dosing label to include dosing regimens for patients with hyperkalemia undergoing stable hemodialysis. The European Commission is expected to make its approval decision in the near future.

In China, Lokelma (sodium zirconium cyclosilicate for oral suspension) was approved in January 2020 for the treatment of hyperkalemia in adults. After a nearly 60-year gap in pharmacological treatments for hyperkalemia, the approval of Lokelma as the first innovative drug launched in China marks the dawn of a new era in the management of hyperkalemia in the country.

Previously, there were no effective therapeutic agents in China capable of rapidly controlling serum potassium while maintaining long-term stability.Lokelmathe efficacy and safety in patients with hyperkalemia worldwideClinical TrialExtensively confirmed in pharmacodynamic studies in China. Study data show that Lokelma begins to take effect within 1 hour of administration, with a median time of 2.2 hours to achieve normal serum potassium levels, and 98% of patients reaching normal serum potassium levels within 48 hours. Nearly 90% of patients maintained serum potassium <5.1 mmol/L over one year of treatment, and safety during 28 days of continuous treatment was comparable to placebo, with good tolerability observed over one year of treatment.

In the first half of 2019, sodium zirconium cyclosilicate for oral suspension was included in the second batch of the “List of Overseas New Drugs in Urgent Clinical Need” by the Center for Drug Evaluation (CDE) of the National Medical Products Administration, granting it priority review and approval, due to its unique mechanism of action and clinical efficacy in addressing unmet treatment needs for patients with hyperkalemia. (Bioon.com)

Original Source: LOKELMA US Label Updated to Include Dosing Guidance for the Treatment of Hyperkalemia in Patients With End-Stage Renal Disease on Hemodialysis