Ardelyx Announces Positive Second Data Analysis from Ongoing NORMALIZE Phase 4 Study Evaluating Tenapanor in CKD Patients on Dialysis
FREMONT, Calif., June 15, 2020 /PRNewswire/ --Ardelyx Inc.. (Nasdaq: ARDX), a specialized biopharmaceutical company focused on developing first-in-class medicines to improve treatment for people with kidney and cardiovascular diseases, today reported positive data from its ongoing NORMALIZE study, which is designed to evaluate the ability of tenapanor, as monotherapy or in combination with sevelamer, to achieve serum phosphorus levels in the normal range (2.5 – 4.5 mg/dL) in patients with chronic kidney disease (CKD) on dialysis. Tenapanor is an investigational, first-in-class, phosphate absorption inhibitor which, if approved, will provide a completely new approach for the control of serum phosphorus in patients with CKD on dialysis, blocking the absorption of phosphorus at the primary pathway of uptake.
"These data from the NORMALIZE study are unprecedented in terms of the proportion of patients able to achieve serum phosphorus levels < 4.6mg/dL with foundational use of tenapanor," said Stuart Sprague DO, FASN, chief of the Division of Nephrology and Hypertension at Northshore University Health System. "This represents an important advancement in the management of hyperphosphatemia for patients on dialysis. The ability of tenapanor to drive phosphorus levels closer to normal has the potential to completely change the hyperphosphatemia treatment paradigm."
The NORMALIZE extension study allowed patients from PHREEDOM, the positive Phase 3 long-term monotherapy study, to continue therapy with tenapanor, and enabled those in the safety control arm receiving sevelamer, to transition to tenapanor. The planned second analysis demonstrated that the foundational use of tenapanor as monotherapy or in combination with sevelamer carbonate produces a significant phosphorus-lowering effect with a mean serum phosphorous reduction of 2.33 mg/dL, from a mean baseline phosphorus of 7.27 mg/dL at the beginning of the PHREEDOM trial to a mean of 4.94 mg/dL at the time of this analysis. Of the 171 patients in this interim analysis who completed up to 9 months of treatment in this extension study, up to 47.4% achieved a normal serum phosphorus level, and of those, the majority were on tenapanor alone or tenapanor with low dose sevelamer of ≤3 sevelamer tablets per day. These data represent a 58% improvement in the rate of patients who achieve a normal serum phosphorus level, as compared to current treatment practice data as reported in the April 2020 Dialysis Outcomes Practice Patterns Study (DOPPS) Practice Monitor. The DOPPS data demonstrate that, with current standard of care treatment of phosphate binders alone, only 30% of patients have serum phosphorous levels < 4.6 mg/dL. The only adverse event reported in >5% of patients in NORMALIZE was diarrhea, with an incidence rate of 23.3%.
Separately, Kyowa Kirin Co., Ltd., a Japan-based global specialty pharmaceutical company exclusively developing tenapanor in Japan, presented results from a Phase 2 trial of tenapanor at the European Renal Association-European Dialysis and Transplant Association annual meeting (ERA-EDTA 2020). The abstract was entitled:
A Phase 2 Open-label, Single-arm, First Japanese Study of Tenapanor, a Novel Phosphate Absorption Inhibitor, Focusing on Pill Burden Decrease in Patients with Hyperphosphatemia Undergoing Hemodialysis.
The trial was designed to evaluate if, with tenapanor, patients could achieve at least a 30% decrease in mean pill burden while maintaining their serum phosphorus level. The study results were statistically significant, with 71.6% (p<0.001) of patients achieving at least a 30% reduction in mean pill burden. The overall mean reduction in phosphate binder usage was 80% (reduction from 14.7 to 3.0 pills per day), while maintaining serum phosphorus control. The mean phosphorus level of patients entering the study on treatment with binders was 5.2 mg/dL at baseline and 4.7 mg/dL at the end of the 26-week study.
"The compelling results of the NORMALIZE study enhance our robust dataset demonstrating tenapanor's ability to significantly decrease serum phosphorous levels, both as a monotherapy and as part of a dual mechanism approach with phosphate binders," said David Rosenbaum, Ph.D., chief development officer of Ardelyx. "The Phase 2 data reported by our partner in Japan, Kyowa Kirin, shows that with tenapanor we are able to control serum phosphorus with a reduced pill burden as compared to treatment with binders. Together, these data continue to advance our understanding of tenapanor and its potential as a transformative treatment for patients with hyperphosphatemia. Of note, we are in the final stages of preparing our New Drug Application for tenapanor for the control of serum phosphorus, which is on track to be submitted mid-year."
NORMALIZE Study Design
Patients entering the study from the tenapanor arm with serum phosphorus levels in the normal range are followed with no medication changes. Patients entering the study from the tenapanor arm with serum phosphorus > 4.5 mg/dL have sevelamer tablets added incrementally to achieve normal serum phosphorus levels. Patients entering the study from the sevelamer safety control arm have tenapanor tablets added to their treatment regimen while reducing sevelamer tablets based on their serum phosphorus value, to achieve normal serum phosphorus levels.
The primary objective of the study is to evaluate the ability of tenapanor alone or in combination with sevelamer to achieve serum phosphorus levels within the normal range (2.5 to 4.5 mg/dL) in patients with chronic kidney disease on dialysis whose serum phosphorus levels were greater than 6.0 mg/dL at baseline.
Kyowa Kirin's Phase 2 Study Design
About Tenapanor for Hyperphosphatemia
About Ardelyx, Inc.
Forward Looking Statements
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Company Codes: NASDAQ-NMS:ARDX