Ardelyx Submits NDA for Tenapanor

Ardelyx announced the submission of a New Drug Application (NDA) for tenapanor to the U.S. Food and Drug Administration (FDA) for the control of serum phosphorus in adult patients with chronic kidney disease (CKD) on dialysis.

"The submission of our NDA is a significant milestone for Ardelyx, positioning us well to fulfill our promise to offer an innovative first-in-class therapeutic for patients with CKD on dialysis with elevated serum phosphorus," said Mike Raab, president and chief executive officer of Ardelyx. "The clinical results we've generated throughout the development program support the potential for tenapanor to serve as the foundational therapy in the management of hyperphosphatemia based on its unique mechanism of blocking phosphorus at the primary pathway of uptake. In addition to the positive monotherapy results demonstrated in our trials, our NORMALIZE and AMPLIFY trials have demonstrated that with tenapanor alone or with adjunctive use of phosphate binders, a far greater percentage of patients are able to achieve, and maintain, target serum phosphorus levels – a goal which has proven to be unattainable for the majority of patients with currently available treatments. We look forward to working with the FDA through the review process and will continue advancing our preparations for launch."

The submission is supported by three successful Phase 3 trials involving over 1,000 patients that evaluated the use of tenapanor, which included: two monotherapy trials, including a long-term study, to control serum phosphorus in patients with CKD on dialysis, and one trial using a dual-mechanism approach in dialysis patients who had difficult-to-control hyperphosphatemia (≥5.5 mg/dL) despite phosphate binder therapy.

Tenapanor, discovered and developed by Ardelyx, is a first-in-class, proprietary, oral medicine for which the company has submitted an NDA to the FDA for the control of serum phosphorus in adult 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 a conformational change of the epithelial cell junctions, thereby significantly reducing paracellular uptake of phosphate at the primary pathway of phosphate absorption. Three successful Phase 3 studies demonstrating tenapanor's ability to reduce phosphate levels, as monotherapy and as part of a dual mechanism approach with phosphate binders, have been reported.

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 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).