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Abstract: TH-OR18

Tenapanor Controls Serum Phosphorus and Reduces PTH and FGF-23 in Patients on Dialysis with Severe Secondary Hyperparathyroidism

Session Information

Category: Bone and Mineral Metabolism

  • 402 Bone and Mineral Metabolism: Clinical

Authors

  • Weiner, Daniel E., Dialysis Clinic Inc, Boston, Massachusetts, United States
  • Spiegel, David M., Ardelyx Inc, Fremont, California, United States
  • Yang, Yang, Ardelyx Inc, Fremont, California, United States
  • Rosenbaum, David P., Ardelyx Inc, Fremont, California, United States
Background

Secondary hyperparathyroidism (sHPT) is common in patients with chronic kidney failure, and most nephrologists treat parathyroid hormone (PTH) values >600 pg/mL. Hyperphosphatemia may directly contribute to sHPT, making the glands less responsive to therapy. Tenapanor is a first-in-class phosphate absorption inhibitor (PAI) that targets the paracellular pathway, the primary pathway of phosphate absorption.

Methods

The phase 3 PHREEDOM trial evaluated the safety and efficacy of tenapanor in patients on dialysis with hyperphosphatemia. Following washout from binders, patients whose serum phosphorus (sP) increased by 1.5 to ≥6.0 mg/dL were randomized. Those randomized to the tenapanor arm received tenapanor 30 mg PO BID for 26 weeks. Serum calcium (sCa), sP, PTH, and FGF23 were measured per protocol. This post-hoc analysis evaluates changes in PTH, FGF23, sP, and sCa among tenapanor-treated patients with baseline PTH >600 pg/mL and at least one post-baseline PTH measure (n=73).

Results

For the 73 participants with severe sHPT (defined as >600 pg/mL), the median baseline PTH was 766 pg/mL with a median absolute (percent) reduction of 280 pg/mL (34.0%) at week 26. Of these 73 patients, 31 had a recorded change in PTH-modifying medication during the treatment period, whereas 42 did not have any recorded change. Among those with medication changes, median PTH reduction was 231 pg/mL (26.9%); among those without changes, PTH reduction was 300 pg/mL (35.4%). Median baseline FGF23 was 15,275 ng/L with a median reduction of 3165 ng/L (40.7%) at the end of the treatment period. The magnitude of the median reductions was similar in the medication change and non-change subgroups (4278 ng/L [40.9%] and 2730 ng/L [38.7%], respectively). On average, sP decreased by 1.8 mg/dL (from 8.0±1.5 mg/dL at baseline), with similar changes in medication change and non-change subgroups (1.9 mg/dL and 1.8 mg/dL, respectively). sCa remained unchanged overall (0.2 mg/dL) and in the medication change and non-change subgroups (0 mg/dL and 0.3 mg/dL, respectively).

Conclusion

Tenapanor effectively lowers sP in patients on maintenance dialysis with severe sHPT and demonstrates that effective sP control with tenapanor improves both PTH and FGF23 concentrations.

Funding

  • Commercial Support