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Abstract: PO0374

Efficacy of Tenapanor for the Control of Serum Phosphorus in Patients with CKD on Dialysis: Novel Mechanism of Action Allows for Both Monotherapy and Dual-Mechanism Approach

Session Information

Category: Bone and Mineral Metabolism

  • 402 Bone and Mineral Metabolism: Clinical

Authors

  • Rosenbaum, David P., Ardelyx Inc, Fremont, California, United States
  • Yang, Yang, Ardelyx Inc, Fremont, California, United States
Background

Tenapanor (TEN) is an investigational, first-in-class, non-binder, phosphate absorption inhibitor being developed to control serum phosphorus (sP) in patients with chronic kidney disease (CKD) on dialysis. It 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 epithelial cell junctions, reducing paracellular uptake of phosphate, the primary pathway of phosphate absorption, thereby reducing serum phosphorus concentrations.

Methods

Two Phase 3 studies were completed. An 8-week, double-blind (DB), randomized treatment period (RT) with a 4-week placebo (PBO)-controlled randomized withdrawal period (RW) examining the efficacy of TEN as monotherapy to treat hyperphosphatemia (HP) in patients with CKD on dialysis (NCT03427125) and a 4-week, randomized, DB, PBO-controlled study examining the efficacy of TEN administered with phosphate binders (BIND) using a dual mechanism approach to treat patients with uncontrolled HP (≥5.5. mg/dL) in patients with CKD on dialysis (NCT 03824587).

Results

In the monotherapy study, 219 patients were randomized to the RT, 164 patients (75%) completed the RT, and of these, 152 (93%) completed the RW. TEN achieved the primary endpoint with a LS mean difference of -0.8 (95% CI: -1.4, -0.2, p=0.01) in sP between TEN and PBO during the RW period. Approximately 50% of the patients treated with TEN achieved a mean sP reduction of 2.56 mg/dL from baseline to the end of the RT period. In the dual mechanism study, 236 patients were randomized to treatment. At week 4, the mean change in sP was significantly greater in the TEN+BIND arm (-0.84 mg/dL v. -0.19 mg/dL in the PBO+BIND arm, p=0.0004). Twice as many patients achieved sP<5.5 mg/dL with TEN+BIND than with PBO+BIND (up to 49.1% v. up to 23.5%, p<0.01). In both studies, the most common adverse event for patients treated with TEN was loose stools/diarrhea, leading to discontinuation in 7.8% and 3.4% of patients respectively.

Conclusion

Results from two DB PBO-controlled clinical trials have demonstrated the potential utility of tenapanor: 1. as effective monotherapy to treat HP in patients with CKD on dialysis, and 2. with phosphate binders for a dual mechanism approach in patients with CKD on dialysis who have difficult to treat HP.

Funding

  • Commercial Support