Coppell, Texas-based biopharmaceutical company ZS Pharma announced the end of patient recruitment for its second phase 3 clinical trial of the drug ZS-9, the ZS004 study. Composed of sodium zirconium cyclosilicate, ZS-9 is a novel investigational treatment for hyperkalemia and results are planned for late in the third quarter or early fourth quarter this year.
ZS004 is a randomized, double-blind, placebo-controlled study, during which the company is evaluating the safety and tolerability of ZS-9 in patients with hyperkalemia. Thanks to fast patient enrollment, ZS Pharma expects to be able to present the full data at medical conferences this year and file a New Drug Application with the United States Food and Drug Administration and a Marketing Authorization Application with the European Medicines Agency in the first half of 2015.
“Completion of enrollment in ZS004 is a key step in advancing the ZS-9 global development program toward planned NDA and MAA submissions in the first half of 2015,” said the Chief Executive Officer of ZS Pharma, Robert Alexander, Ph.D. “It also brings us one step closer to potentially making ZS-9 available to patients who need new treatment options for hyperkalemia.”
A total of 258 patients at 42 participating sites have been enrolled in the ZS004 trial, which was initiated in March 2014. It includes patients with hyperkalemia (potassium levels >5 mEq/L), as well as with chronic kidney disease (CKD), heart failure, and diabetes on renin angiotensin aldosterone system (RAAS) inhibitor therapy. During the global multicenter, multi-dose, prospective, randomized, double-blind, placebo-controlled clinical trial, patients are administered with 10g of ZS-9, three times per day, for 48 hours.
In case of normokalemia, which means potassium levels between 3.5 and 5 mEq/L, patients become eligible for the randomized, double-blind trial to one of three doses of ZS-9 (5g, 10g or 15g) or placebo administered once-daily tests, for a withdrawal period of 28 days. ZS Pharma investigators will primarily compare the mean serum potassium level of each ZS-9 treatment group and compare it with the placebo group over the randomized withdrawal period.
ZS004’s main purpose is to assess the safety and efficacy of the drug and confirm, over a longer treatment period, the positive results verified in the ZS003 trials, in which it was demonstrated that once-daily doses of ZS-9 maintain potassium levels within the normal range with safety and tolerability similar to placebo. Preliminary findings from ZS004 were also already presented at the 74th American Diabetes Association (ADA) Scientific Sessions last month. The trials showed the drug’s ability to rapidly reduce serum potassium in hyperkalemic patients to normal levels within 48 hours, as well as control the normal potassium range throughout the 12-day Extended Treatment Phase.
ZS Pharma is conducting a ZS004E trial as well, which is an extension study that aims to develop longer-term open-label safety, tolerability, and efficacy data in patients who participated in ZS004. Patients will be treated for five months with ZS-9 to complete the ZS004E trial.
ZS-9 was designed to treat severe and chronic hyperkalemia, a life-threatening metabolic condition that can lead to cardiac arrhythmia and sudden cardiac death regardless of underlying cause. The disease is characterized by abnormally high concentrations of potassium in the blood resulting from the inability of the kidneys to excrete potassium, impairment of mechanisms that transport potassium into cells, or a combination of both factors.
ZS Pharma recently received Notices of Allowance from the U.S. Patent and Trademark Office (USPTO) for two patent applications regarding the drug that cover both methods of treating the disease as well as the composition, carrying term to at least 2032.