Abstract: PO0384
Long-Term Safety and Efficacy of Tenapanor for the Control of Serum Phosphorus in Patients with CKD on Dialysis
Session Information
- Biochemical Aspects of Mineral and Bone Disease
October 22, 2020 | Location: On-Demand
Abstract Time: 10:00 AM - 12:00 PM
Category: Bone and Mineral Metabolism
- 402 Bone and Mineral Metabolism: Clinical
Authors
- Chertow, Glenn Matthew, Stanford Medicine, Stanford, California, United States
- Yang, Yang, Ardelyx, Inc., Fremont, California, United States
- Rosenbaum, David P., Ardelyx, Inc., Fremont, California, United States
Background
Tenapanor (TEN) is an investigational, first-in-class, non-binder therapy that targets the primary pathway of phosphate absorption, providing a novel approach to treating hyperphosphatemia. TEN blocks the paracellular absorption of phosphate in the GI tract by local inhibition of the sodium-hydrogen exchanger (NHE3) and is dosed as one small pill (<12x7 mm) twice daily. Two previously conducted pivotal trials of TEN met their primary efficacy endpoint.
Methods
A 52-week study consisting of a 26-week, open-label, randomized treatment period (RT) with a 12-week placebo-controlled randomized withdrawal period (RW), followed by a 14-week open label safety extension period (SE). Patients on maintenance dialysis with serum phosphorus (sP) ≥ 6.0 mg/dL and <10.0 mg/dL and a 1.5 mg/dL increase in sP following washout were randomized 3:1 to receive one 30 mg TEN tablet BID or sevelamer carbonate (SEV; a safety control) dosed per package insert. At end of RT all patients in the TEN arm were re-randomized 1:1 to either TEN or placebo for the RW. Primary endpoint was the mean change in sP from the end of RT to the end of the RW and was compared between TEN and placebo for the efficacy analysis set, defined as patients demonstrating a ≥ 1.2 mg/dL decrease in sP at the end of RT.
Results
The study achieved its primary endpoint demonstrating a statistically significant difference in least squares (LS) mean sP change (-1.4 mg/dL, p<0.0001), between TEN and placebo. For the efficacy analysis set (n=131), the mean sP decreased from 7.7 mg/dL at baseline to 5.1 mg/dL at the end of the 26-week TEN treatment, with a mean reduction of 2.6 mg/dL. During the 26-week treatment period, 77% of TEN-treated patients in the intent-to-treat population (n=407) had a decrease in sP, with a mean reduction from baseline of 2.0 mg/dL. TEN was generally well tolerated; the only AE with incidence >5% during RT was loose stools/diarrhea (53.0%), the majority of which were mild-to-moderate and transient in nature. In the RT, 17.4% of tenapanor-treated patients compared to 23.4% of sevelamer-treated patients experienced a serious adverse event.
Conclusion
The trial results suggest that among patients on maintenance dialysis with hyperphosphatemia, TEN dosed one tablet twice daily is safe and efficacious as monotherapy.
Funding
- Commercial Support –