Positive top-line results announced from HAEMONIZE (ZS004), a second Phase 3 clinical trial of ZS-9 in patients with hyperkalemia

ZS Pharma, a biopharmaceutical company developing novel treatments for kidney, cardiovascular, liver and metabolic disorders, has announced positive top-line results from HARMONIZE (ZS004), its second Phase 3 clinical trial of ZS-9 (sodium zirconium cyclosilicate), a novel investigational treatment for hyperkalemia. Preliminary analyses of the results showed that all three doses (5g, 10g, and 15g) of once daily ZS-9 met the primary endpoint, demonstrating that ZS-9 prevented recurrence of hyperkalemia when compared with placebo over a 28-day treatment period. Safety, tolerability and adverse events are generally consistent with previous ZS-9 clinical studies. The data will be presented at the American Heart Association Scientific meeting in November during the late-breaking Clinical Science Special Reports Session.

"With the completion of the HARMONIZE trial, we remain on track to submit NDA and MAA filings for ZS-9 in the first half of 2015. Importantly, our clinical experience with ZS-9 now includes nearly 1000 patients, some of whom have been treated with ZS-9 for over 5 months," said Robert Alexander, Ph.D., Chief Executive Officer of ZS Pharma, "We are excited to announce these preliminary results and look forward to having the lead study investigator, Mikhail Kosiborod, M.D., share the full data at a late-breaking session at the American Heart Association meeting."

HARMONIZE (ZS004) Phase 3 Study Design

The HARMONIZE (HyperkAlemia RandoMized interventiON multI-dose ZS-9 maintEnance) study is a global, prospective, randomized, double-blind, placebo-controlled trial that enrolled 258 patients with hyperkalemia with no upper limit on serum potassium (K+) at entry. Patients included those with chronic kidney disease (CKD), heart failure (HF), diabetes and those on renin angiotensin aldosterone system (RAAS) inhibitor therapy. In the open-label induction phase of the study, patients received 10g of ZS-9 administered three times daily for 48 hours and were monitored to establish the speed and magnitude of serum potassium reduction. Patients who achieved normokalemia (K+ levels between 3.5 and 5 mEq/L) were randomized in a double-blind fashion to one of three doses of ZS-9 (5g, 10g or 15g) or placebo administered once-daily for 28 days (the randomized withdrawal period). The primary efficacy endpoint compared the mean serum K+ level of each ZS-9 treatment group to that of placebo over the interval between day 8 and day 28 of the randomized withdrawal period. Patients who completed the initial 28-day maintenance phase were eligible to enroll in an ongoing open label extension study, ZS004E.

About ZS-9's Clinical Development Program

The ZS-9 clinical program is designed to investigate the treatment of acute and chronic hyperkalemia, regardless of underlying cause. ZS Pharma has completed ZS003, a 753-patient Phase 3 study, which showed that ZS-9 rapidly reduced serum potassium in hyperkalemic patients to normal levels within the 48-hour Acute Phase and then controlled potassium in the normal range throughout the 12-day Extended Treatment Phase. In addition, the study provided evidence suggesting that ZS-9 is well tolerated with an adverse event profile similar to placebo.

HARMONIZE, the Company's second Phase 3 clinical trial of ZS-9, is a randomized, double-blind, placebo-controlled study designed to confirm, over a longer treatment period, the positive results observed in ZS003. In conjunction with HARMONIZE, ZS Pharma is also conducting ZS004E, an extension study that will generate longer-term open-label safety and tolerability data in patients who participated in HARMONIZE. The Company is conducting an additional long-term safety study, ZS005, designed to evaluate the ability of ZS- 9 to restore and maintain normal serum potassium levels in patients with hyperkalemia over at least one year of dosing.

The Company plans to file a New Drug Application (NDA) with the United States Food and Drug Administration and a Marketing Authorization Application (MAA) with the European Medicines Agency in the first half of 2015.

About Hyperkalemia

Hyperkalemia, or higher than normal potassium levels (typically defined as a serum potassium level >5 mEq/L), is a potentially life-threatening metabolic condition that can lead to cardiac arrhythmia and sudden cardiac death. Hyperkalemia 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. The causes of hyperkalemia vary but the most common are chronic kidney disease (CKD), diabetes, heart failure (HF) and side effects from cardio-renal protective drug therapy, such as renin angiotensin aldosterone system (RAAS) inhibitors.