Ardelyx has announced that its Phase 3 trial of tenapanor, a novel treatment for hyperphosphatemia in patients with end-stage renal disease (ESRD) on dialysis, met its primary endpoint of significant difference in serum phosphorus levels.
Tenapanor, a first-in-class, oral medication, works by blocking the NHE3 sodium transporter in the gastrointestinal (GI) tract, reducing the absorption of dietary sodium resulting in increased protons within the cells. The increase in protons causes a selective reduction in phosphate uptake by tightening junctions that regulate phosphate absorption in the GI tract. Tenapanor is minimally absorbed and is designed to work only within the GI tract, reducing the potential for side effects.
The Phase 3 trial lasted for 8 weeks and included a total of 164 ESRD patients with hyperphosphatemia who were randomized to three separate dosing arms; 3mg or 10mg twice-daily, and 30mg twice-daily with the option to down-titrate once a week during the first 4 weeks to 20, 15, 10 and 3mg twice-daily. After the 8 week treatment period, patients were re-randomized 1:1 to remain on their current tenapanor dose or switch to placebo for a 4 week, randomized withdrawal period.
The responder population, defined as patients who demonstrated a ≥1.2mg/dL decrease in serum phosphorus from baseline during the 8 weeks, was 80 out of 164. Results demonstrated a statistically significant difference in serum phosphorus levels from the end of the 8 week treatment period to the end of the 4 week randomized withdrawal period between the tenapanor group and the placebo group (mean –1.01 mg/dL, median of –1.3 mg/dL), meeting the trials primary endpoint (95% CI –1.44, –0.21; LSmean –0.82 mg/dL; P=0.01).
“These data validate tenapanor’s unique mechanism of action and its potential to be the first non-phosphate binder treatment for this difficult-to-manage disorder,” said Geoff Block, MD, director, clinical research at Colorado Kidney Care, and an investigator in the trial.
Ardelyx is planning a second Phase 3 trial to last for 26 weeks, for later this year, with full details of final trial design currently under consultation.
For more information visit Ardelyx.com.