FDA Approves Tenapanor for Treatment of Chronic Kidney Disease

The FDA has approved tenapanor (Xphozah; Ardelyx, Inc.), making it the first and only phosphate absorption inhibitor approved to reduce serum phosphorus in adults with chronic kidney disease (CKD) who are on dialysis as adjunctive therapy in patients who either do not respond to phosphate binders or who are intolerant to any dose of phosphate binder therapy. This unique tablet is taken twice daily and offers a first-in-class mechanism of action that blocks the absorption of phosphate through its primary pathway, according to a press release from Ardelyx.

Tenapanor is a first-in-class phosphate absorption inhibitor with a differentiated mechanism of action that acts in the intestine. It hinders the sodium-hydrogen exchanger 3 (NHE3), thereby reducing the absorption of phosphate along the paracellular pathway, which is the main route of phosphate absorption.

Managing hyperphosphatemia poses a persistent clinical challenge because the majority of patients receiving maintenance dialysis are unable to consistently achieve target serum phosphate concentrations despite treatment with phosphate binders, said Glenn Chertow, MD. , MPH, professor of medicine at Stanford University, in a press release. . [Tenapanor] is not a phosphate binder. [Tenapanor] is an inhibitor of phosphate absorption. In patients not responding adequately to treatment with phosphate binders, [tenapanor] It has been shown to help increase the proportion of patients achieving target serum phosphate concentrations. I believe [tenapanor] can advance the management of patients with hyperphosphatemia, by offering a new treatment option with a complementary mechanism of action.

The FDA approval is the result of 3 phase 3 clinical trials PHREEDOM, BLOCK and AMPLIFY which evaluated the efficacy and safety of tenapanor as monotherapy and in combination with phosphate therapy. All 3 trials met their primary and secondary endpoints while demonstrating that tenapanor significantly reduced serum phosphorus elevations in patients receiving maintenance hemodialysis. Additionally, there are 2 open clinical trials, OPTIMIZE and NORMALIZE, which have evaluated different options for integrating Tenapanor into clinical practice.

The most common adverse reaction (AE) observed in patients in the trials was diarrhea, which occurred shortly after treatment initiation in 43% to 53% of patients and at least 5% in patients with CKD treated with tenapanor and on dialysis throughout the trials. Most reported events were mild to moderate in severity and resolved with time or dose reduction. Severe diarrhea was less common and was reported in only 5% of patients treated with Tenapanor across trials. Tenapanor is not recommended in pediatric patients younger than 6 years or in patients with known or suspected mechanical gastrointestinal obstruction.

The approval of [tenapanor] is an important step for dialysis patients, their families and the nephrology care community, as it represents a new mechanism and a new option for patients who, despite treatment with phosphate binders, continue to have a rate of high phosphorus, Mike Raab, CEO and President of Ardelyx. , said in the press release. This approval is also a tribute to the patients, families, physicians and clinical trial staff who participated in the development of [tenapanor]. There is a high level of anticipation and excitement for the launch of [tenapanor] of the renal community, and [Ardelyxs] A world-class team will enter the market well-positioned with a best-in-class product.

Reference

Ardelyx. FDA approves XPHOZAH (tenapanor), a first-in-class phosphate absorption inhibitor. Press release. October 17, 2023. Accessed October 18, 2023. https://ir.ardelyx.com/news-releases/news-release-details/fda-approves-xphozahr-tenapanor-first-class-phosphate-absorption