ZS Pharma (Nasdaq: ZSPH), a biopharmaceutical company developing novel treatments for kidney, cardiovascular, liver and metabolic disorders, today presented detailed results from HARMONIZE (ZS004) at the late-breaking Clinical Science Special Reports Session of the American Heart Association Scientific Sessions. HARMONIZE is the second positive Phase 3 clinical trial of ZS-9 (sodium zirconium cyclosilicate) for the treatment of hyperkalemia, a life threatening condition characterized by abnormally high concentrations of potassium in the blood (serum K+ ≥5.1 mEq/L). In addition to the presentation, the study results were simultaneously published today in The Journal of the American Medical Association (JAMA).
The HARMONIZE trial met the primary efficacy endpoint by demonstrating that all three doses (5g, 10g, and 15g) of once daily ZS-9 maintained mean potassium at lower levels than placebo over the 28-day treatment period (p-value ≤0.0001 all doses) with significantly higher proportions of patients having mean serum potassium (K+) levels in the normal range while on ZS-9 than placebo (80 percent, 90 percent, and 94 percent at the 5, 10 and 15g dose, respectively, compared with 46 percent on placebo). In the open-label acute phase, serum potassium levels declined from 5.6 mEq/L at baseline to 4.5 mEq/L with 98 percent of patients achieving normokalemia within 48 hours of beginning treatment. Time to onset of activity with ZS-9 was rapid with the median time to normokalemia of 2.2 hours. Responses were larger in patients with severe hyperkalemia (K+ ≥6.0 mEq/L), with mean changes of -0.5 mEq/L at one hour, -0.7 mEq/L at two hours, and -1.5 mEq/L at 48 hours. The adverse events with the highest rates in HARMONIZE were anemia, constipation, edema, hypokalemia, nasopharyngitis, and upper respiratory tract infections.
“Today’s HARMONIZE 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 an extended period,” said Mikhail N. Kosiborod, M.D., cardiologist at Saint Luke's Mid America Heart Institute and University of Missouri-Kansas City, and the lead clinical investigator in the HARMONIZE trial. “I believe that these results have the potential to shift the current paradigm for how hyperkalemia is managed among various at-risk patient groups, including patients on RAASi therapy.”
“The Phase 3 results suggest that ZS-9, if approved, could be an effective, well-tolerated, and much needed treatment for hyperkalemia,” said Robert Alexander, Ph.D., Chief Executive Officer of ZS Pharma.