Ardelyx Announces Positive Second Data Analysis from Ongoing NORMALIZE Phase 4 Study Evaluating Tenapanor in CKD Patients on Dialysis
"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
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
Separately, Kyowa Kirin Co., Ltd., a
A Phase 2 Open-label, Single-arm, First Japanese Study of Tenapanor, a Novel Phosphate Absorption Inhibitor, Focusing on Pill
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
NORMALIZE Study Design
Patients completing the Phase 3 PHREEDOM trial from both the tenapanor arm and the sevelamer safety control arm had the option to participate in NORMALIZE, an ongoing open-label 18-month extension study.
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
A multicenter, open-label, single-arm Phase 2 study consisted of a screening period, a 3-week observation period, and a 26-week treatment period. Patients whose serum phosphorus level was 3.5 to 7.0 mg/dL, taking at least two phosphate binder pills three times a day were enrolled. Patients received 30 mg of tenapanor twice daily. Phosphate binder treatment was continued according to individual regimens; however, the dose was adjusted to maintain serum phosphorus level within ±0.5 mg/dL from baseline. The primary endpoint was the achievement of at least a 30% decrease in the mean total number of phosphate binder and tenapanor pills compared to the number of phosphate binder pills at baseline.
About Tenapanor for Hyperphosphatemia
Tenapanor, discovered and developed by
Hyperphosphatemia is a serious condition resulting in an abnormally elevated level of phosphorus in the blood that is estimated to affect more than 745,000 dialysis patients in major developed countries. The kidney is the organ responsible for regulating phosphorus levels, but when kidney function is significantly impaired, phosphorus is not adequately eliminated from the body. As a result, hyperphosphatemia is a nearly universal condition among people with CKD and especially those on dialysis. Despite treatment with phosphate binders (the only approved therapy for hyperphosphatemia), approximately 70% of CKD patients on dialysis continue to experience elevated phosphorus levels at any point in time (Spherix Global Insights: RealWorld Dynamix, Dialysis 2018). Phosphorus levels greater than 5.5 mg/dL have been shown to be an independent risk factor for cardiovascular morbidity and mortality in patients requiring dialysis (Block 2004), and internationally recognized treatment guidelines recommend lowering elevated phosphate levels toward the normal range (<4.6mg/dL).
Forward Looking Statements
To the extent that statements contained in this press release are not descriptions of historical facts regarding
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