Abstract: TH-PO162
Reduction of Serum Phosphorus (sP) With Tenapanor (TEN) in Patients With CKD on Dialysis With Severe Hyperphosphatemia
Session Information
- CKD-MBD: Targets and Outcomes
November 03, 2022 | Location: Exhibit Hall, Orange County Convention Center‚ West Building
Abstract Time: 10:00 AM - 12:00 PM
Category: Bone and Mineral Metabolism
- 402 Bone and Mineral Metabolism: Clinical
Authors
- Sprague, Stuart Michael, NorthShore University HealthSystem-University of Chicago Pritzker School of Medicine, Chicago, Illinois, United States
- Yang, Yang, Ardelyx, Inc., Waltham, Massachusetts, United States
- Spiegel, David M., Ardelyx, Inc., Waltham, Massachusetts, United States
- Rosenbaum, David P., Ardelyx, Inc., Waltham, Massachusetts, United States
Background
TEN is a first-in-class, investigational phosphate absorption inhibitor (PAI) that blocks paracellular phosphate absorption in the gastrointestinal tract by local inhibition of intestinal NHE3, providing a novel approach to managing hyperphosphatemia. TEN met the primary sP-lowering endpoint in 2 phase 3 monotherapy trials (BLOCK [NCT02675998], PHREEDOM [NCT03427125]) and was generally well tolerated. In patients with CKD, the risk of cardiovascular (CV) morbidity and mortality increases as sP levels increase. We evaluated the effect of TEN in patients with CKD on dialysis with severe hyperphosphatemia (≥7.5 mg/dL) from BLOCK and PHREEDOM.
Methods
BLOCK had an 8-week open-label randomized treatment period (RTP; 3, 10, or 30 mg TEN twice a day [bid] dose titration), followed by a 4-week placebo-controlled randomized withdrawal period (RWP). PHREEDOM had a 26-week open-label RTP (30 mg TEN bid dose titration), followed by a placebo-controlled RWP of up to 12 weeks and a 14-week open-label safety extension. Both studies enrolled patients on maintenance dialysis with sP ≥6.0 and ≤10.0 mg/dL and an sP increase ≥1.5 mg/dL after phosphate binder washout. During the RTP of each study, we evaluated sP reduction (to last assessment during RTP) in patients with baseline sP ≥7.5 mg/dL.
Results
In BLOCK, 107/215 patients in the intent-to-treat (ITT) analysis set had a baseline sP ≥7.5 mg/dL across the 3 dose groups; these patients had a mean sP ±SD reduction of 1.78 ±1.73 mg/dL from baseline to the end of the RTP, and the 37 patients from the 30 mg dose group had a 1.91 ±1.83 mg/dL sP reduction. In PHREEDOM, 204/407 patients in the ITT analysis sets had a baseline sP ≥7.5 mg/dL; these patients had a mean sP ±SD reduction of 1.94 ±1.86 mg/dL. During the RTPs of both studies, the only adverse event reported in >10% of patients with severe hyperphosphatemia in the safety analysis sets was diarrhea (BLOCK, 43.1%; PHREEDOM, 51.2%), which led to study drug discontinuation in 6.4% and 17.7%, respectively.
Conclusion
Tenapanor, a novel investigational PAI dosed as a single twice-daily tablet, provides a clinically meaningful sP reduction with an acceptable safety profile for patients with severe hyperphosphatemia on dialysis who are at high risk of CV morbidity and mortality.
Funding
- Commercial Support –