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Abstract: TH-PO1187

Efficacy of Tenapanor in Combination with Phosphate Binders in CKD Patients on Dialysis with Uncontrolled Hyperphosphatemia While on Phosphate Binders Alone

Session Information

Category: Bone and Mineral Metabolism

Authors

  • Pergola, Pablo E., Renal Associates, P.A., San Antonio, Texas, United States
  • Yang, Yang, Ardelyx, Fremont, California, United States
  • Rosenbaum, David P., Ardelyx, Inc., Fremont, California, United States
  • Chertow, Glenn Matthew, Stanford University School of Medicine, Palo Alto, California, United States
Background

Tenapanor (TEN) is a first-in-class, non-binder, phosphate absorption inhibitor being developed to treat hyperphosphatemia in dialysis patients. 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 the epithelial cell junctions, reducing paracellular uptake of phosphate, the primary pathway of phosphate absorption, and thereby reducing serum P concentrations.

Methods

4-week, randomized, double-blind, placebo (PBO)-controlled study with a 2 to 4-week standard of care run-in period. Patients on maintenance dialysis, on stable phosphate binder (BIND) therapy who had a serum P≥5.5 and ≤10.0 mg/dL at screening and the end of the run-in period were randomized 1:1 to receive TEN+BIND or PBO+BIND. Patients’ dose of BIND remained stable during both washout and treatment periods. The primary endpoint was the change from baseline in serum P at week 4 between the TEN+BIND and PBO+BIND arms. (NCT 03824587)

Results

511 patients were screened, and 236 patients were randomized to treatment. Mean age was 54.5 years, 58.9% male, 49.6% white, 43.2% Black, BMI 32.1 kg/m2. Mean (±SD) baseline P was 6.73±1.32 mg/dL and 6.93±1.37 mg/dL for TEN+BIND and PBO+BIND groups respectively. At week 4, the mean change in serum P was more pronounced in the TEN+BIND arm (-0.84 mg/dL v. -0.19 mg/dL in the PBO+BIND arm, p=0.0004). When added to BIND therapy, TEN resulted in statistically significant decreases in serum P during all four weeks of treatment ranging from 0.84 to 1.21 mg/dL. Twice as many patients achieved P<5.5 mg/dL with TEN+BIND than with PBO+BIND (up to 49.1% v. up to 23.5%, p<0.01). TEN+BIND resulted in a 24% relative reduction in serum intact FGF23 (p=0.0027) at week 4. For patients on TEN, the only adverse event with a placebo-adjusted rate over 3% was loose stools/diarrhea (36%); 4.3% of patients discontinued the study while on TEN+BIND v. 2.5% on PBO+BIND. There were no serious adverse events related to TEN.

Conclusion

In patients on dialysis who have uncontrolled phosphorus despite BIND treatment, adding TEN results in improvement in P levels and a significantly higher percentage of patients achieving phosphorus levels <5.5 mg/dL.

Funding

  • Commercial Support