Positive top-line Phase III for ZS Pharma's hyperkalemia drug
This article was originally published in Scrip
ZS Pharma has reported positive top-line results from the initial 'acute' part of a pivotal Phase III trial of its lead drug candidate ZS-09, a new treatment for hyperkalemia, at the ASN Kidney Week 2013 annual meeting in Atlanta, GA, over the weekend.
Preliminary top-line analyses of the acute part of the ZS-003 trial showed that it met its primary endpoint of a rapid, significant reduction in serum potassium (K+) over the initial 48 hours.
ZS-9 is an oral sorbent designed to trap potassium ions over other ions throughout the gastrointestinal tract. The inorganic crystal is administered as a tasteless, odorless powder or tablet.
However, ZS is trailing Relypsa, which said last month that it is getting ready to file an NDA for its hyperkalemia drug candidate patiromer (RLY5016) following positive Phase III data (scripintelligence.com, 11 October 2013). The two drugs have similar mechanisms of action.
Relypsa also presented data at the ASN Kidney Week meeting, supporting the company's earlier disclosure of significant topline efficacy results in both Part A and Part B of its two-part pivotal Phase III trial evaluating patiromer.
ZS's clinical program for ZS-9 is designed to investigate treatment of acute, subacute and chronic hyperkalemia. The company plans to initiate an additional Phase III trial, the ZS-004 trial, in early 2014, to evaluate it for extended use. This randomized, double-blind, placebo-controlled trial is designed to confirm, using a month-long dosing period, the optimal dose of ZS-9 for extended treatment.
ZS-003 details
ZS-003 was a randomized, double-blind, placebo-controlled pivotal Phase III trial that enrolled 753 patients with hyperkalemia (potassium levels 5-6.5 mEq/L), including patients with chronic kidney disease (CKD), heart failure, diabetes, and those on renin angiotensin aldosterone system (RAAS) inhibitor therapy.
Patients were randomized to receive one of four doses of ZS-9 (1.25g, 2.5g, 5g or 10g) or placebo, administered three times daily for the initial 48 hours (acute phase). The primary endpoint was the rate of change in serum K+ from baseline throughout the 48 hour acute phase, which was the same primary endpoint used in the ZS-002 study. Patients normalized in the acute phase were then randomized to active drug (1.25g, 2.5g, 5g or 10g) or placebo administered once-daily for 12 days (the subacute phase). The secondary endpoint for the randomized withdrawal subacute phase was the rate of change in serum K+ during the 12-day dosing period.
Data from the subacute phase will be released in the coming months, said the company.
Top-line preliminary results from the acute phase showed significant, rapid, and dose-dependent reductions in serum K+ at the 2.5g, 5g, and 10g doses compared with placebo, meeting the primary efficacy endpoint for the acute phase (p=0.0009, <0.0001, and=""><0.0001 respectively).="" mean="" serum="" k+="" reduction="" was="" -0.73="" meq/l="" at="" the="" 10g="" dose="" at="" 48="" hours=""><0.0001), 14="" hours="" after="" the="" last="" dose.="">
In addition, ZS-9 was well tolerated. Across all doses, the incidence of adverse events was similar to placebo. Specifically, the gastrointestinal adverse event rate was 3.5% in patients receiving ZS-9 compared with 5.1% for those on placebo.
The new data were presented by Dr Stephen Ash of Indiana University Health Arnett, during the ASN Kidney Week 2013, being held this week.
Elevated potassium levels in the blood can lead to fatal arrhythmia. People with renal impairment, hypertension, diabetes and heart failure have a higher risk for hyperkalemia. The condition is a common side effect of RAAS inhibitors prescribed for CKD and heart failure.