WASHINGTON—In dialysis patients with uncontrolled hyperphosphatemia despite phosphate binder therapy, the addition of tenapanor may reduce serum phosphate levels, according to late-breaking research presented at the American Society of Nephrology’s Kidney Week 2019.
In a double-blind trial (NCT 03824587), Glenn M. Chertow, MD, MPH, of Stanford University in Palo Alto, California, and colleagues randomly assigned 236 patients on maintenance dialysis (mean age 54.5 years; 58.9% male; 43.2% black) with uncontrolled serum phosphate (5.5 to 10.0 mg/dL) despite a stable dose of phosphate binder to receive either add-on tenapanor or placebo.
Tenapanor is a novel phosphate absorption inhibitor that blocks sodium-hydrogen exchanger 3 in the intestine. This tightens epithelial cell junctions and thereby reduces paracellular uptake of phosphate.
At baseline, the mean phosphate concentration was 6.73 vs 6.93 mg/dL for tenapanor and placebo recipients, respectively. Over 4 weeks, serum phosphate declined significantly more in the tenapanor plus phosphate binder group: -0.84 vs -0.19 mg/dL. Twice as many tenapanor than placebo recipients achieved serum phosphate levels less than 5.5 mg/dL: up to 49.1% vs up to 23.5%, respectively. The addition of tenapanor also significantly reduced serum intact fibroblast growth factor 23 by 24% by week 4.
No serious adverse events were reported during the trial. A third of tenapanor recipients experienced loose stools/diarrhea, which is slightly more than placebo recipients. Overall, 4.3% of tenapanor and 2.5% placebo patients discontinued the trial.
The study was funded by Ardelyx, the makers of tenapanor.
“Tenapanor has completed two Phase 3 trials, demonstrating the ability of tenapanor as a monotherapy and in combination with phosphate binders, to statistically, significantly reduce serum phosphorus in dialysis patients,” according to a statement from Ardelyx.
The company is conducting an additional long-term phase 3 monotherapy study of tenapanor called PHREEDOM, which is expected to be completed in the fourth quarter of 2019.
Pergola PE, Yang Y, Rosenbaum D, Chertow GM. Efficacy of tenapanor in combination with phosphate binders in CKD patients on dialysis with uncontrolled hyperphosphatemia while on phosphate binders alone. Presented at the American Society of Nephrolog’s Kidney Week 2019 meeting held November 5 to 10, 2019, in Washington DC. Late-breaking abstract TH-PO1187.
Tenapanor for Hyperphosphatemia. Ardelyx. Accessed on December 9, 2019 at https://ardelyx.com/what-we-do/