AstraZeneca Submits Lokelma (Sodium Zirconium Cyclosilicate) for Approval in China as Part of Its Renal Portfolio Expansion

Today (July 10), the official website of the Center for Drug Evaluation of the National Medical Products Administration showed that AstraZeneca's application for marketing authorization of sodium zirconium cyclosilicate powder (Lokelma) for hyperkalemia in China has been accepted, with the acceptance number JXHS1900098.

Lokelma is a highly selective oral potassium binder that is tasteless and stable at room temperature. The drug was originally developed by ZS, and AstraZeneca acquired the development rights to this potential blockbuster drug after acquiring ZS for $2.7 billion in November 2015.

LokelmaApproved by the European Commission in March 2018 and by the U.S. FDA in May 2018 for the treatment of hyperkalemia in adult patients.In China, Lokelma was included in the second batch of overseas drugs urgently needed for clinical use released by the Center for Drug Evaluation of the National Medical Products Administration at the end of March this year. The reason for its inclusion was that "the only existing treatment options are sodium polystyrene sulfonate and calcium polystyrene sulfonate, which fail to meet clinical needs, whereas Lokelma offers clinical advantages."

Significant Clinical Efficacy

Hyperkalemia (serum potassium levels >5.0 mEq/L) typically occurs in patients with advanced kidney disease and/or chronic heart failure, potentially leading to cardiac arrest and death. The risk of hyperkalemia is significantly increased in patients with chronic kidney disease (CKD) and those taking common heart failure (HF) medications, such as renin-angiotensin-aldosterone system (RAAS) inhibitors, as these drugs elevate serum potassium levels. Currently, treatment options for hyperkalemia are limited, indicating a substantial unmet medical need in this field.

LokelmaRegarded as a best-in-class treatment for hyperkalemia, Lokelma has been demonstrated through a series of studies to reduce serum potassium levels in patients with chronic kidney disease, heart failure, diabetes, and those taking RAAS inhibitors.

The U.S. FDA approval of Lokelma was based on data from three double-blind, placebo-controlled trials and two open-label trials. The data demonstrated that the onset of action of Lokelma occurred 1.0 hour after administration, the median time to achieve normal serum potassium levels was 2.2 hours, 92% of patients achieved normal serum potassium levels within 48 hours post-baseline, and the therapeutic effect was maintained for up to 12 months.

In June 2019, AstraZeneca announced positive data from the DIALIZE Phase IIIb clinical study of Lokelma, which evaluated the efficacy and safety of Lokelma in treating hyperkalemia in patients with end-stage renal disease (ESRD) on stable dialysis. The results showed that 41.2% of patients treated with Lokelma maintained normal pre-dialysis serum potassium levels (4–5 mmol/L) after a prolonged interdialytic period, compared to only 1.0% in the placebo group.

Because the dosing regimen used in the trial has not yet been approved, data from the DIALIZE study will support the label update for Lokelma in the United States.

# Renal Disease Flagship Products Gather in China

Early this year, AstraZeneca China announced the restructuring of its Cardiovascular, Renal and Metabolism (CVRM) Business Unit, formally dividing it into three therapeutic areas: cardiovascular, renal, and diabetes and metabolism.

On May 30, AstraZeneca announced that Alex Lin from Ping An Good Doctor would join the company as Assistant Vice President of AstraZeneca China, overseeing the renal therapeutic area, effective June 3, 2019. In his new role as head of the renal therapeutic area, Mr. Lin will be fully responsible for AstraZeneca China’s renal business. He will lead the renal team to ensure the commercial launch of roxadustat and build a team for Lokelma, a novel drug for hyperkalemia in kidney disease that serves as the second pillar product in AstraZeneca China’s renal portfolio, driving its approval and commercial launch.

It is evident that the core of AstraZeneca China’s business in the nephrology therapeutic area is clearly defined—Roxadustat and Lokelma.

Roxadustat (brand name: Evrenzo^®As the world’s first oral hypoxia-inducible factor prolyl hydroxylase inhibitor (HIF-PHI), it received marketing approval from the National Medical Products Administration in December 2018 for the treatment of anemia in patients with chronic kidney disease (CKD) on dialysis, including those undergoing hemodialysis and peritoneal dialysis. Notably, roxadustat is the first globally innovative original drug with a novel mechanism of action to be initially approved in China, achieving three “firsts” and marking a milestone innovation. It is understood that roxadustat is scheduled to be launched in the second half of this year, and Sina Medicine will continue to closely follow its specific commercialization plans.

Following in the footsteps of roxadustat, Lokelma has also officially entered the approval process and is included on the List of Overseas New Drugs Urgently Needed for Clinical Use. It is believed that the market launch of Lokelma in China will be further accelerated.

We also look forward to this new drug bringing effective treatment options to this patient population in China as soon as possible.

References:

Lin Xiao Joins AstraZeneca to Lead Renal Therapeutics https://med.sina.com/article_detail_100_1_66687.html

AstraZeneca’s New Potassium-Lowering Drug Lokelma Approved: Rapid Onset and Sustained Efficacy https://med.sina.com/article_detail_103_2_46155.html