Sodium zirconium cyclosilicate (ZS-9) is an orally administered, non-absorbed, novel, inorganic microporous compound that was engineered to preferentially entrap excess potassium ions in a highly selective manner. We believe that the high potassium (K+) specificity and rapid onset of action of ZS-9 is attributable to its chemical composition and design, which mimics the body’s own physiologic K+ channels and selectively filters potassium throughout the gastrointenstinal tract without impacting other cations such as calcium, magnesium, and sodium.
In contrast, sodium polystyrene sulfonate (SPS), Kayexalate, the only approved treatment for hyperkalemia in the United States, is a nonselective, organic polymer resin. The potassium selectivity and binding capacity of ZS-9 remains unaffected by the presence of other competing cations, unlike nonselective, organic polymer resins. Head-to-head in vitro comparisons demonstrate that ZS-9 has a 9.3-fold higher potassium binding capacity than SPS. In the Company’s clinical studies, this selectivity has resulted in the following important differentiating characteristics of ZS-9, supporting its potential use to treat acute and chronic hyperkalemia:
- Rapid Onset
- In all clinical trials to date, ZS-9 led to a rapid, and predictable decline in serum potassium, with statistically significant reductions in potassium 1 hour after the first dose of ZS-9.
- In patients with potassium levels above 6 mEq/L, serum potassium reductions were -0.5, and -0.7 at 1 and 2 hours, respectively.
- High Response Rates and Predictable Potassium Control:
- In a recently completed Phase 3 clinical trial (HARMONIZE), the median time to normalization was 2.2 hours after a single dose of ZS-9 (normal levels of potassium in the blood; K+ between 3.5 and 5.0 mEq/L). Eighty four percent (84%) of patients normalized within 24 hours and 98% of patients achieved normokalemia within 48 hours.
- Maintenance of Normal Potassium Levels with Once Daily Dosing:
- In two phase 3 studies, 5g and 10g of once daily ZS-9 maintained normokalemia and prevented recurrence of hyperkalemia when compared to placebo.
- Equivalent Efficacy Across Patient Subgroups:
- ZS-9 achieved a significant mean reductions in K+ and prevented return in hyperkalemia in all patients, as well as the heart failure (HF), diabetes mellitus (DM), chronic kidney disease (CKD) and renin-angiotensin aldosterone system inhibitor (RAASi) pre-defined subgroups within 48 hours
- ZS-9 Appeared to be Well Tolerated
- Gastrointestinal side effects occurred at a similar rate as placebo across all studies.
- The adverse event rates were similar across placebo and ZS-9 treated subjects and consistent in all pre-defined subgroups (HF, CKD, DM, and RAASi)
- No clinically significant effects on other electrolytes that are critical for normal physiological functioning, including sodium, calcium and magnesium
- Does not appear to have drug-drug interaction with any common CKD or HF medications, including common RAASi therapies
- Easily taken as a convenient oral suspension powder or tablets
- Stability at room temperature with a long shelf-life, which may simplify distribution, physician sampling and storage for both physicians and patients
January 6, 2015
ZS Pharma to Present at J.P. Morgan Healthcare ConferenceDownload PDF
November 21, 2014
ZS Pharma Announces Publication of Results from Phase 3 Study of ZS-9 in Patients with Hyperkalemia in the New England Journal of MedicineDownload PDF
November 17, 2014
ZS Pharma Presents Positive Results from HARMONIZE (ZS004), a Second Phase 3 Clinical Trial of ZS-9 in Patients with Hyperkalemia, at the American Heart Association Scientific Meeting and Announces Simultaneous Publication of Results in JAMADownload PDF