Ardelyx Announces Successful Phase 3 Trial of Tenapanor for Hyperphosphatemia in Patients with End-Stage Renal Disease
Key Trial Results
The responder population (n=80 out of 164) had a mean reduction in serum phosphorus from baseline to the end of the eight-week treatment period of 2.56 mg/dL, with a reduction of up to 5.7 mg/dL. Notably, in this group, 33 percent of patients had a reduction in serum phosphorus of greater than 3 mg/dL. The study demonstrated a statistically significant difference in serum phosphorus levels from the end of the eight-week treatment period to the end of the four-week randomized withdrawal period between the tenapanor-treated group and the placebo-treated group in the responder patient population (mean -1.01 mg/dL, median of -1.3 mg/dL) and met its primary endpoint (95% CI -1.44, -0.21; LSmean -0.82 mg/dL; p=0.01). Only 7.8 percent of patients discontinued treatment due to GI side effects.
Hyperphosphatemia is a condition of higher than normal levels of serum phosphorus in the blood that is estimated to affect more than 745,000 people with ESRD who are on dialysis in major developed countries1.
"The reduction in serum phosphorus in many patients treated with tenapanor is remarkable. These data validate tenapanor's unique mechanism of action and its potential to be the first non-phosphate binder treatment for this difficult-to-manage disorder," said
"We are very pleased with the overall efficacy and improved tolerability profile of tenapanor in this study. The magnitude of the reduction of serum phosphorus in a large percentage of patients treated with tenapanor in this trial surpassed our expectations," said
Tenapanor was well-tolerated in the trial. In the eight-week treatment period, the only adverse event that affected more than five percent of patients treated with tenapanor was diarrhea (39 percent), a patient-reported side effect of loosened stool or increased frequency in bowel movements regardless of magnitude. In the four-week randomized withdrawal period, there was a diarrhea rate of 1.2 percent for patients treated with tenapanor compared with 2.4 percent on placebo. Treatment discontinuations due to diarrhea for patients treated with tenapanor was 7.8 percent (n=17). There were no discontinuations due to diarrhea in the randomized withdrawal period.
In order to fully assess GI tolerability, patients used an eDiary to record the frequency of daily bowel habits, as well as stool form using the Bristol Stool Form Scale (BSFS). During the eight-week treatment period, there was a 0.4 per day increase in bowel movement frequency from baseline, and during the four-week randomized withdrawal period, there was a 0.29 per day increase as compared to placebo. Bowel movement frequency was within the normal range in all groups.
During the eight-week treatment period, there was a 0.87 point increase in BSFS from a baseline score of 4.2, out of a maximum of seven, where seven is liquid stool. During the four-week randomized withdrawal period, there was a 0.7 point difference in BSFS between placebo (4.4) and tenapanor treatment (5.1).
Second Phase 3 Trial
The results from this trial support
"What is particularly exciting about these data is the innovation that we are bringing to patients on dialysis who have relied on the available binder treatments for decades," said Dr.
About the Trial
The Phase 3 trial was an eight-week, double-blind, randomized trial, with a four-week placebo-controlled randomized withdrawal period.
The primary endpoint of the trial is the difference in change in serum phosphorus between the pooled tenapanor-treated patients and placebo-treated patients from the end of the eight-week treatment period to the end of the four-week randomized withdrawal period, in the responder population. The responder population, which was reviewed by the
Tolerability endpoints included stool consistency as measured by the Bristol Stool Form Scale and frequency.
About Tenapanor for Hyperphosphatemia
Tenapanor is a first-in-class, proprietary, oral, experimental medication in late-stage clinical development. It has a unique mechanism of action that works exclusively in the gut. In hyperphosphatemia, tenapanor blocks the NHE3 sodium transporter in the GI tract, reducing the absorption of dietary sodium and resulting in increased protons within the cells. The increase in protons causes a selective reduction in phosphate uptake by tightening junctions or pores that regulate phosphate absorption in the GI tract. These effects are selective without impacting transport of other ions, nutrients or macromolecules, and consistent with our observations in clinical trials. Tenapanor is minimally absorbed and has been specifically designed to work exclusively within the GI tract, thereby significantly reducing the potential side effects that could occur.
Hyperphosphatemia is a condition resulting in an abnormally elevated level of phosphorus in the blood that is estimated to affect more than 745,000 people in major developed countries1. Phosphorus is one of the most abundant and essential elements in the body and plays an important role in multiple biological processes. The kidney is the major organ involved in regulating phosphorus levels in the body, but when kidney function is impaired, phosphorus is not excreted adequately from the body. As such, hyperphosphatemia is a common condition associated with end-stage renal disease in people receiving dialysis. There are currently no treatments approved for hyperphosphatemia that are not phosphate binders.
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Forward Looking Statements
To the extent that statements contained in this press release are not descriptions of historical facts regarding
 USRDS 2014; European ERA-EDTA Registry Annual report 2012; Nakai S, et al, 2008
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