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ZS Pharma Announces Positive Interim Results From a Long-Term Safety Study of ZS-9

SAN MATEO, Calif., Nov. 7, 2015 (GLOBE NEWSWIRE) -- ZS Pharma, Inc. (Nasdaq:ZSPH), today presented interim results from ZS005, a long-term safety and efficacy study of ZS-9 (sodium zirconium cyclosilicate), an investigational treatment for hyperkalemia, at a late-breaking poster presentation during the American Society of Nephrology's (ASN) Kidney Week 2015.



"Today's results suggest that in addition to its ability to rapidly lower potassium levels to the normal range, ZS-9 was shown to maintain normal potassium levels over a 12 month period," said James A. Tumlin, M.D., C.C.R.P., Nephrologist, Associate Professor of Medicine at the University of Tennessee Chattanooga, Medical Director of Southeast Renal Research Institute (SERRI) and President, Nephronet, and a clinical investigator in the trial. "This is the largest, long-term hyperkalemia trial conducted to date, and I believe that, if approved, ZS-9 would offer physicians an attractive option for the acute as well as chronic management of hyperkalemia."

ZS005 Phase 3 Interim Results

The poster entitled Long-Term (52-Week) Efficacy and Safety of ZS-9 in the Treatment of Hyperkalemia: Interim Results From a Phase 3 Open-Label, Multi-Center, Multi-Dose Maintenance Study, contains the results as of October 10, 2015 of the first 711 patients enrolled in the ZS005 study. Mean potassium levels at baseline in the study were 5.6 mEq/L with over 60 percent of patients having baseline potassium levels ≥5.5 mEq/L. As of October 10, 507 patients completed at least 3 months of therapy, 353 patients completed at least 6 months of therapy, 216 patients completed at least 9 months of therapy, and 69 patients completed 12 months of ZS-9 treatment.

ZS005 Efficacy Results

  • Ninety-nine percent (99%) of patients achieved normokalemia in the Acute Phase on 10 grams TID of ZS-9
  • Mean potassium levels were maintained at 4.6 mEq/L throughout the 12 month Long Term Treatment Phase
  • The primary efficacy endpoint was met with 87 to 92 percent of patients maintained at an average serum potassium ≤5.1 mEq/L between month 3 and month 12
  • Normokalemia was maintained with patients receiving once-daily 5 gram (64%), 10 gram (30%), or 15 gram (5%) doses of ZS-9

Serum potassium data over 52 weeks are summarized here: http://media.globenewswire.com/cache/32050/file/38599.pdf

ZS005 Safety Results

Adverse Events Occurring in ≥5% of Patients, or AEs of Interest (N=684)

Adverse Event (AE) % N
Any event 51.6 353
All Peripheral Edema 7.7 53
Edema requiring treatment 4.2 29
Hypertension 7.0 48
Hypokalemia (Serum K+ = 3.0 to 3.5 mEq/L) 2.5 17
Hypokalemia (Serum K+ < 3.0 mEq/L) 0.0 0
Worsening Chronic Kidney Disease * 0.7 5

* Doubling of serum creatinine

  • There were no deaths in the Acute Phase; 5 deaths (0.7%) occurred in the Long Term Phase but none were considered to be related to study drug
  • The rate of peripheral edema was 53/684 (7.7%); only 29/684 (4.2%) patients required treatment with diuretics
  • 26/29 (90%) patients that required treatment had prior history of edema
  • Exposure corrected rates of edema:
    • 0-6 months = 0.00057
    • 6-12 months = 0.00015
  • No significant change from baseline at 3, 6, 9 and 12 months in weight or blood pressure
  • The rate of hypokalemia (serum K+ <3.5 mEq/L) was 2.5 percent; all cases were mild
  • There were no changes in serum Mg+2, Ca+2, and Na+

Conclusions

  • In patients with hyperkalemia, ZS-9 rapidly normalized serum potassium levels and maintained serum potassium levels at 4.6 mEq/L with once daily treatment for up to 52 weeks, with >90 percent of patients maintained with 5 or 10 grams of ZS-9
  • Improvement in metabolic acidosis was observed and consistent with previous studies
  • Exposure corrected edema rates were consistent with HARMONIZE placebo group (0.00089) and do not increase with duration of ZS-9 therapy
  • Rates of edema and hypertension were consistent with the patient population over this time frame
  • There was a low rate of gastrointestinal (GI) adverse events (<5%) with ZS-9 treatment

ZS005 Phase 3 Study Design

ZS005, a global, multicenter trial designed to investigate the long-term safety and efficacy of ZS-9 in 750 patients with hyperkalemia (potassium levels >5.0 mEq/L) from sites in the U.S., EU, Australia and South Africa. Patients with hyperkalemia receive a 10 gram dose of ZS-9 administered three times daily for until achieving normokalemia during the 24 to 72 hour Acute Phase of the study. Patients that achieve normokalemia then receive a 5 gram dose of ZS-9 administered once-daily with the ability to titrate dose in 5 gram increments or decrements, if needed, to maintain normokalemia. The primary endpoint is safety and tolerability, and the secondary endpoint is the proportion of patients with average serum potassium ≤5.1 mEq/L between Month 3 and Month 12.

About ZS-9 (sodium zirconium cyclosilicate)

ZS-9 is an insoluble, non-absorbed zirconium silicate with a clearly defined three-dimensional crystalline lattice structure that was designed to preferentially trap potassium ions. The potassium selectivity of ZS-9 enables high in-vitro binding capacity for potassium ions even in the presence of other competing ions. ZS-9 has been studied in three double-blind, placebo controlled trials and in two 12 month open-label studies in patients with hyperkalemia. ZS-9 is an investigational product that is not approved by the U.S. Food and Drug Administration (FDA) or European regulatory agencies for any indication.

About Hyperkalemia

Hyperkalemia, or higher than normal potassium levels (typically defined as a serum potassium level > 5.0 mEq/L), is a life-threatening metabolic condition that can lead to cardiac arrhythmia and sudden cardiac death. Hyperkalemia results from the inability of the kidneys to excrete potassium, impairment of mechanisms that transport potassium into cells, or a combination of both factors. The diseases that cause 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.

About ZS Pharma

ZS Pharma is a publicly-traded (Nasdaq:ZSPH), biopharmaceutical company focused on the development and commercialization of highly selective, non-absorbed drugs to treat renal, cardiovascular, liver and metabolic disorders. ZS Pharma's lead therapeutic candidate, ZS-9 (sodium zirconium cyclosilicate), is an investigational agent that has been submitted to the FDA for potential approval for the treatment of hyperkalemia. The ZS-9 Prescription Drug User Fee Act (PDUFA) goal date for a decision by the FDA is May 26, 2016. ZS Pharma is also pursuing the discovery of additional drug candidates that utilize its novel selective ion-trap technology. Additional information about ZS Pharma is available at www.zspharma.com.

Forward-Looking Statements

ZS Pharma cautions you that this press release contains forward-looking statements that involve risks and uncertainties. We make such forward-looking statements pursuant to the safe harbor provisions of the Private Securities Litigation Reform Act of 1995 and other federal securities laws. Any statements contained herein that are not statements of historical facts may be deemed to be forward-looking statements. In some cases, you can identify forward-looking statements by terminology such as "aim," "anticipate," "assume," "believe," "contemplate," "continue," "could," "due," "estimate," "expect," "goal," "intend," "may," "objective," "plan," "predict," "potential," "positioned," "seek," "should," "target," "will," "would" and other similar expressions that are predictions of or indicate future events and future trends, or the negative of these terms or other comparable terminology. These forward-looking statements include, but are not limited to, statements about: our expectations regarding the timing of the review of an NDA by the FDA, submitting an MAA to the EMA, the likelihood of regulatory approval of ZS-9, our expectations regarding our ability to successfully commercialize ZS-9, if approved, estimates of our expenses, future revenue, capital requirements and needs for additional financing, our ability to produce ZS-9 in commercial quantities in higher capacity reactors, the initiation, timing, progress and results of future nonclinical studies, clinical trials and research and development programs, and our financial performance. Any forward looking statements in this press release are based on management's current expectations, estimates, forecasts, and projections about our business and the industry in which we operate and management's beliefs and assumptions are not guarantees of future performance or development and involve known and unknown risks, uncertainties and other factors that are in some cases beyond our control. As a result, any or all of our forward-looking statements in this press release may turn out to be inaccurate. Factors that may cause actual results to differ materially from expectations include, among other things, those listed under Part I, Item 1A. Risk Factors in ZS Pharma's Quarterly Report on Form 10-Q filed with the Securities and Exchange Commission August 6, 2015 and its other reports, which are available from the SEC's website (http://www.sec.gov) and on ZS Pharma's website (http://www.zspharma.com) under the heading "Investors". All forward‐looking statements are qualified in their entirety by this cautionary statement and speak only as of the date of this press release. Except as required by law, we assume no obligation to update or revise these forward-looking statements for any reason, even if new information becomes available in the future. You should, however, review the factors and risks described in the reports we will file from time to time with the SEC after the date of this press release.

CONTACT: ZS Pharma Contacts Myesha Edwards (Investors) ZS Pharma 650.753.1854 medwards@zspharma.com Denise Powell (Media) Red House Consulting 510.703.9491 denise@redhousecomms.com

Source:ZS Pharma

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