COPPELL, Texas--(BUSINESS WIRE)--ZS Pharma, a specialty pharmaceutical company developing novel treatments for kidney, cardiovascular and liver disorders, today announced top-line results from the Acute Phase of its pivotal Phase 3 ZS-003 trial of ZS-9, a novel, investigational treatment for hyperkalemia. Preliminary top-line analyses of the safety and efficacy results of the Acute Phase showed that the trial met its primary endpoint, demonstrating a rapid, statistically significant reduction in serum potassium (K+) over the initial 48 hours. These results confirm the positive results demonstrated in the Phase 2 trial (ZS-002), a multicenter, double-blind, placebo-controlled study, which also met its primary efficacy endpoint. The results of both of these clinical trials support the safety and efficacy of ZS-9 in treating hyperkalemia, regardless of underlying cause. The data were presented by Stephen R. Ash, M.D., of Indiana University Health Arnett, during the High-Impact Clinical Trials Oral Session at ASN's Kidney Week 2013.
"Hyperkalemia is a serious medical condition associated with significantly increased mortality rates, but physicians lack a safe and reliable therapy to lower serum K+ levels"
"Hyperkalemia is a serious medical condition associated with significantly increased mortality rates, but physicians lack a safe and reliable therapy to lower serum K+ levels," said Dr. Ash. "ZS-9 shows promise as an effective, well tolerated, fast-acting, and predictable treatment for patients with hyperkalemia."
ZS-003 Phase 3 Trial Design and Preliminary Top-Line Results
ZS-003 was a randomized, double-blind, placebo-controlled pivotal Phase 3 clinical 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.
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.
- The trial met the primary efficacy endpoint for the Acute Phase at the 2.5g, 5g, and 10g doses compared with placebo (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 (p<0.0001), 14 hours after the last dose.
- ZS-9 was well tolerated. Across all doses, the incidence of adverse events was similar to placebo. Specifically, the gastrointestinal (GI) adverse event rate was 3.5 percent in patients receiving ZS-9 compared with 5.1 percent for those receiving placebo.
Additional results from the ZS-003 trial, including the Subacute Phase, are expected in the coming months.
"The preliminary Phase 3 study results are promising and I look forward to additional Phase 3 results as they become available," said Dr. Geoff Block, director of clinical research at Denver Nephrology, associate clinical professor in medicine at the University of Colorado Health Sciences Center and a clinical investigator in the ZS-003 study. "There is a critical need for a new treatment for patients with hyperkalemia, including those with chronic kidney disease, diabetes, heart failure and those who should be on cardio-renal protective treatment such as ACEs and ARBs."
ZS-002 Phase 2 Trial Design and Results
ZS-002 was a first-in-man, proof-of-concept Phase 2 trial that assessed the safety and efficacy of ZS-9 in treating hyperkalemia in patients with chronic kidney disease (CKD). This double-blind, placebo-controlled trial enrolled 90 patients with Stage 3 CKD and mild to moderate hyperkalemia (serum K+ levels of 5-6 mEq/L) and randomized them into four different cohorts to receive either placebo (n=30) or one of three doses of ZS-9 given orally three times daily (0.3g [n=12], 3g [n=24], and 10g [n=24]). The primary endpoint was the rate of change in serum K+ levels from baseline through 48 hours.
ZS-9 demonstrated significant, rapid and dose-dependent reductions in serum K+ and met the primary efficacy endpoint at the 10g and 3g doses compared with placebo (p<0.0001 and p=0.048, respectively).
- Within the first 48 hours after treatment initiation, 63 percent of patients in the 10g group had ≥1.0 mEq/L reduction in serum K+ compared with 17 percent who received placebo.
- Maximum mean reduction in serum K+ was 0.92 mEq/L lower than baseline at 38 hours (p<0.0001), four hours after the last dose, and 0.68 mEq/L lower at 48 hours (p<0.0001), 14 hours after last dose.
- Maximum mean serum K+ reduction was -0.92 mEq/L at 38 hours (p<0.0001), four hours after the last dose and -0.68 mEq/L at 48 hours (p<0.0001), 14 hours after the last dose.
- A subanalysis of patients receiving concomitant renin angiotensin aldosterone system (RAAS) inhibitor therapies demonstrated serum K+ reductions consistent with the overall population.
- ZS-9 was well tolerated. No serious adverse events were reported, and no patients withdrew from the study due to adverse events.
About the ZS-9 Clinical Development Program
The ZS-9 clinical program is designed to investigate treatment of acute, subacute and chronic hyperkalemia. The Company plans to initiate an additional Phase 3 trial, the ZS-004 trial, in early 2014. 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.
Hyperkalemia, or higher than normal potassium levels (typically defined as a serum potassium level >5 mEq/L), is a 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. Causes of hyperkalemia can vary; however, most hyperkalemia is a consequence of renal disease, diabetes, heart failure, hypertension or side effects from cardio-renal protective drug therapy, such as renin angiotensin aldosterone system (RAAS) inhibitors. The rise in chronic medical conditions commonly associated with hyperkalemia highlight an unmet medical need for a therapy that is safe, rapid and predictable, and offers a favorable side effect profile.
ZS Pharma is a privately held specialty pharmaceutical company based in Coppell, Texas. ZS Pharma's lead therapeutic candidate, ZS-9, is in Phase 3 clinical trials. It is being developed to treat hyperkalemia, a potentially life-threatening metabolic condition characterized by an abnormally high serum concentration of potassium. ZS Pharma is also pursuing the discovery of additional drug candidates that utilize its novel selective ion-trap technology for the treatment of kidney and liver diseases. Additional information is available at www.zspharma.com.