The investigational nonbinder tenapanor shows efficacy and safety over more than 6 months for patients with hyperphosphatemia, investigators reported at Kidney Week 2020 Reimagined, a virtual meeting sponsored by the American Society of Nephrology.
Glenn M. Chertow, MD, MPH, of Stanford University in Palo Alto, California, and colleagues performed a 52-week study, PHREEDOM, consisting of a 26-week, open-label, randomized treatment period with a 12-week placebo-controlled randomized withdrawal period, followed by a 14-week open-label safety extension period. Patients on maintenance dialysis with serum phosphorus of 6.0 or higher but less than 10.0 mg/dL and a 1.5 mg/dL increase in serum phosphate following washout were randomized 3:1 to receive 30 mg tenapanor twice daily or sevelamer carbonate (for control). Following the intervention period, patients receiving tenapanor were re-randomized 1:1 to receive either tenapanor or placebo for the withdrawal period.
Serum phosphate significantly decreased by a least squares mean of 1.37 mg/dL (P <.0001), with tenapanor vs placebo, Dr Chertow’s team reported. In an efficacy analysis involving 131 patients, mean serum phosphate decreased from 7.7 mg/dL at baseline to 5.1 mg/dL after 26 weeks, with a mean reduction of 2.6 mg/dL. In the intent-to-treat population of 407 patients, 77% of tenapanor-treated patients experienced a mean reduction in serum phosphate of 2.0 mg/dL.
“The trial results suggest that among patients on maintenance dialysis with hyperphosphatemia, tenapanor dosed one tablet twice daily is safe and efficacious as monotherapy,” Dr Chertow and colleagues stated. “Treatment with tenapanor resulted in clinically meaningful and sustained reductions in serum phosphorus levels owing to the novel mechanism of action of tenapanor that blocks the paracellular absorption of phosphate.”
In PHREEDOM, a total of 17.4% of tenapanor-treated patients and 23.4% of sevelamer-treated patients experienced a serious AE.
A second study presented at Kidney Week examined the tolerability of tenapanor across 3 trials, including PHREEDOM, TEN201, a 12-week monotherapy study, and AMPLIFY, a 4-week combination study. The only adverse event that occurred in more than 5% of tenapanor-treated patients was diarrhea in 53.0%, 47.9%, and 42.7%, respectively, during the treatment period. Diarrhea incidence during the withdrawal period was 4.0% vs 1.6% in PHREEDOM and 2.9% vs 2.4% in TEN201 for the tenapanor vs placebo groups.
Across all studies, tenapanor-associated diarrhea was mostly mild-to-moderate and transient and typically resolved within 2 weeks. Approximately 5% of patients experienced severe diarrhea. In TEN201, mean stool frequency increased by 2.8 bowel movements per week over baseline, and stool consistency increased by 0.8 points using the 7-poin Bristol stool form scale, both remaining within the normal range.
“These results demonstrate that tenapanor is associated with few [gastrointestinal] side effects,” Stuart M. Sprague, DO, of NorthShore University HealthSystem in Evanston, Illinois, and colleagues concluded.
Disclosure: These studies were supported by Ardelyx, Inc. Please see the original reference for a full list of authors’ disclosures.
Chertow GM, Yang Y, Rosenbaum DP. Long-term safety and efficacy of tenapanor for the control of serum phosphorus in patients with CKD on dialysis. Presented at: Kidney Week 2020 Reimagined; October 19-25, 2020. Abstract PO0384.
Rosenbaum DP, Sprague SM. Tolerability of tenapanor, an investigational, first-in-class, non-binder therapy for the control of serum phosphorus in patients with CKD on dialysis. Presented at: Kidney Week 2020 Reimagined; October 19-25, 2020. Abstract PO0376.