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

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

“Hyperphosphatemia management has been a persistent clinical challenge, as 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, Stanford University, in a press release. “[Tenapanor] is not a phosphate binder. [Tenapanor] is a phosphate absorption inhibitor. In patients not adequately responding to phosphate binder therapy, [tenapanor] has been shown to help increase the proportion of patients achieving target serum phosphate concentrations. I believe [tenapanor] can advance the care of patients with hyperphosphatemia, providing a new treatment option with a complementary mechanism of action.”

The FDA approval is a result of 3 phase 3 clinical trials—PHREEDOM, BLOCK, and AMPLIFY—that evaluated the efficacy and safety of tenapanor as both a monotherapy and a combination treatment with phosphate bunder therapy. The 3 trials had met their primary and key secondary endpoints, while demonstrating that tenapanor significantly reduced elevated serum phosphorus in patients receiving maintenance hemodialysis. Further, there are 2 open-label clinical trials, OPTIMIZE and NORMALIZE, that evaluated different options for integrating tenapanor into clinical practice.

The most common adverse effect (AE) patients experienced in the trials was diarrhea, which occurred soon after initiation in 43% to 53% of patients and at least 5% in tenapanor-treated patients with CKD on dialysis throughout the trials. Most of the occurrences were reported to be mild to moderate in severity and had resolved over time or with dose reduction. Severe diarrhea was less common and only reported in 5% of tenapanor-treated patients across the trials. Tenapanor is not recommended for pediatric patients under 6 years of age or patients with known or suspected mechanical gastrointestinal obstruction.

“The approval of [tenapanor] is an important milestone for patients on dialysis, their families, and the nephrology care community, as it represents a new mechanism and new option for patients who, despite treatment with phosphate binders, continue to have elevated 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 personnel who participated in the development of [tenapanor]. There is a high level of anticipation and enthusiasm for the launch of [tenapanor] from the kidney community, and [Ardelyx’s] world-class team will enter the marketplace well positioned with a first-in-class product.”

Reference

Ardelyx. FDA Approves XPHOZAH® (tenapanor), a First-in-Class Phosphate Absorption Inhibitor. News 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