Ardelyx reported positive results from AMPLIFY, a phase III study of tenapanor in combination with phosphate binders in patients with chronic kidney disease (CKD) on dialysis whose hyperphosphatemia was not previously controlled with binders alone. The AMPLIFY study met the primary endpoint and all key secondary endpoints, including demonstrating a statistically significant reduction in serum phosphorus levels for patients treated with tenapanor and phosphate binders compared to phosphate binders alone.
AMPLIFY, a double-blind, placebo-controlled, randomized study, enrolled a total of 236 patients with CKD on dialysis who, despite a stable phosphate binder regimen, had a serum phosphorus level greater than or equal to 5.5 mg/dL and less than or equal to 10.0 mg/dL at screening. After a run-in of two to four weeks, patients were randomized 1:1 to receive tenapanor or placebo twice daily while continuing their established phosphate binder regimen. Baseline serum phosphorus at randomization was at a mean level of 6.8 mg/dL. Tenapanor was initiated at a starting dose of 30 mg twice daily with tenapanor dose adjustments allowed based on serum phosphorus level and gastrointestinal tolerability. The primary endpoint of the study was the comparison of the change from baseline in serum phosphorus levels at week four between the tenapanor and binder arms.
Patients treated in the tenapanor/binder arm had a statistically significant mean reduction in serum phosphorus from baseline to the end of the four-week treatment period of 0.84 mg/dL, as compared to those treated in the placebo/binder who had a mean reduction of 0.19 mg/dL. The key secondary endpoints were reached too, including the proportion of patients achieving a serum phosphorus level below 5.5 mg/dL at week four and relative change from baseline in FGF23 levels between the tenapanor and binder arms at week four.
Tenapanor is a first-in-class, proprietary oral medicine. Tenapanor has a unique mechanism of action and acts locally in the gut to inhibit the sodium hydrogen exchanger 3 (NHE3). This results in the tightening of the epithelial cell junctions, thereby significantly reducing paracellular uptake of phosphate, the primary pathway of phosphate absorption.
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 common 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 over time. Phosphorus levels greater than 5.5 mg/dL have been shown to be an independent risk factor for cardiovascular morbidity and mortality in dialysis patients and common treatment goals are to manage serum phosphorus levels to <5.5mg/dL.Source: Ardelyx