On September 3, 2019, Ardelyx, Inc. (the “Company” or “Ardelyx”), a specialized biopharmaceutical company focused on developingfirst-in-class medicines to improve treatment for people with cardiorenal diseases, reported positive results from AMPLIFY, a pivotal Phase 3 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 (p=0.0004) reduction in serum phosphorus levels for patients treated with tenapanor and phosphate binders compared to phosphate binders alone. Tenapanor is an investigational,first-in-class, small molecule,non-binder, phosphate absorption inhibitor being developed to treat hyperphosphatemia in patients with CKD on dialysis.
Key Study Results
For the primary endpoint, patients treated in the tenapanor arm (tenapanor in combination with phosphate binders, n=116) had a statistically significant (p=0.0004) 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 binder arm (placebo in combination with phosphate binders, n=119) who had a mean reduction of 0.19 mg/dL. Patients in the tenapanor arm had statistically significant decreases in serum phosphorus during all four weeks ranging from 0.84 to 1.21 mg/dL(p-values<0.0004). During the treatment period, up to 49.1% of patients in the tenapanor arm achieved a serum phosphorus of <5.5 mg/dL which was statistically significant compared with up to 23.5% in the binder arm(p-values£0.0097). There was a statistically significant 22% to 24% reduction(p-values£0.0027) in FGF23 levels in the tenapanor arm as compared to the binder arm. Elevated levels of FGF23 are associated with an increased risk of major cardiovascular events.
Tenapanor was well tolerated. Only 4.3% of patients in the tenapanor arm discontinued treatment compared to 2.5% in the binder arm. The single adverse event with a placebo-adjusted rate greater than 3% was loose stools/diarrhea at 36%, where most incidents were reported within the first five days of treatment, were transient in nature and the median time to resolution was four days after onset. Notably, only 2.6% of patients in the tenapanor arm discontinued treatment due to loose stools/diarrhea, as compared to 0.8% in the binder arm. There were no serious adverse events related to tenapanor.
About AMPLIFY
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 arun-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. The key secondary endpoints included a comparison of 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.
About Tenapanor for Hyperphosphatemia
Tenapanor, discovered and developed by Ardelyx, is afirst-in-class, proprietary, oral, medicine in late-stage clinical development for the control of serum phosphorus in patients with CKD on dialysis. 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. In addition, if approved, tenapanor will be easier than phosphate binders for patients to take with a regimen of just one small pill, taken twice daily. The Company previously reported results from its first Phase 3 monotherapy study with tenapanor in CKD patients on dialysis, reporting that the primary endpoint was met (p=0.01) and that 50% of patients (n=164) experienced a mean serum phosphorus reduction of 2.56 mg/dL.
