Ardelyx said doses of tenapanor, which inhibits controls serum phosphorus by inhibiting the sodium hydrogen exchanger 3 (NHE3), demonstrated a statistically significant reduction in serum phosphorus levels for dialysis patients whose hyperphosphatemia was not previously controlled with phosphate binders alone.
California-based Ardelyx reported its Phase III AMPLIFY study of tenapanor achieved its primary endpoint, as well as all key secondary endpoints in treating patients with chronic kidney disease (CKD).
Ardelyx said doses of tenapanor, which inhibits controls serum phosphorus by inhibiting the sodium hydrogen exchanger 3 (NHE3), demonstrated a statistically significant reduction in serum phosphorus levels for dialysis patients whose hyperphosphatemia was not previously controlled with phosphate binders alone. The trial assessed tenapanor in combination with phosphate binders in comparison to phosphate binders alone. Hyperphosphatemia is a serious condition resulting in an abnormally elevated level of phosphorus in the blood associated with CKD and particularly those on dialysis. Despite treatment with phosphate binders, which is currently the only approved therapy for hyperphosphatemia, approximately 70% of CKD patients on dialysis continue to experience elevated phosphorus levels over time, Ardelyx said.
In the Phase III trial, Ardelyx said patients in the tenapanor arm had statistically significant decreases in serum phosphorus during all four weeks of the study. 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 company said 49.1% of patients in the treatment arm saw a serum phosphorus reduction of less than 5.5 mg/dL, compared to 23.5% in the binder arm. Also, the company said there was a statistically significant 22% to 24% reduction in FGF23 levels in the tenapanor arm as compared to the binder arm. Elevated levels of FGF23, a protein in humans that is responsible for phosphate and vitamin D metabolism, are associated with an increased risk of major cardiovascular events.
Mike Raab, president and chief executive officer of Ardelyx, expressed his excitement in the results from the AMPLIFY study. He said the late-stage data showed tenapanor can help significantly more patients achieve the established serum phosphorus treatment goal of less than 5.5 mg/dL.
“This result is striking as serum phosphorus levels above 5.5 mg/dL are associated with increased mortality. For too long, hyperphosphatemia management has been an enormous challenge for patients and clinicians. With tenapanor, patients may finally be able to achieve their treatment goal,” Raab said in a statement.
Ardelyx plans to take the results from the AMPLIFY study, as well as the pending results from the Phase III PHREEDOM study of tenapanor as a monotherapy and use them for a New Drug Application. The company plans to seek regulatory approval of tenapanor as both a monotherapy and combination treatment for hyperphosphatemia. Ardelyx believes that, if approved, tenapanor can become a foundational therapy for all CKD patients on dialysis who experience elevated serum phosphorus.
“The promising results from AMPLIFY bring us one step closer to providing this important medicine to patients with CKD on dialysis,” Raab added.
Ardelyx is currently awaiting a decision from the U.S. Food and Drug Administration for tenapanor as a treatment for irritable bowel syndrome with constipation (IBS-C). The FDA is expected to make a decision on the NDA for that indication next week. The NDA was based on positive Phase III data that showed patients taking tenapanor had at least a 30 percent reduction in abdominal pain and an increase of one or more complete spontaneous bowel movements in the same week for at least six of the 12 weeks of the treatment period.
In addition to efficacy, the AMPLIFY study also confirmed that tenapanor was well tolerated, with only 4.3% of patients discontinuing treatment compared to 2.5% in the binder arm. The most frequent adverse event was loose stool/diarrhea, which was reported at 36%. 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, Ardelyx said.
