Tenapanor May Improve Phosphate Normalization in the Dialysis Population

In the NORMALIZE study, tenapanor, a novel phosphate absorption inhibitor under review by the FDA, helped to reduce serum phosphate by an additional 2.33 mg/dL, on average, over 18 months, investigators reported.

The novel phosphate absorption inhibitor tenapanor may increase the proportion of patients on dialysis who attain normal serum phosphate levels, investigators reported at the virtual National Kidney Foundation 2021 Spring Clinical meetings.

The finding is from the NORMALIZE extension trial, which included patients who completed the 1-year phase 3 PHREEDOM trial. The study population included 110 patients in the PHREEDOM tenapanor arm of the trial — who received either tenapanor alone or received sevelamer in addition to tenapanor — and 62 patients from the PHREEDOM sevelamer arm — who received tenapanor in addition to their sevelamer dose.

Investigators re-assigned patients to receive either tenapanor as monotherapy or in combination with lower doses of sevelamer, a non-calcium phosphate binder. Serum phosphate declined from a mean 7.27 mg/dL at baseline to 4.94 mg/dL over 18 months, the investigators reported. Further, up to 47.4% of patients achieved serum phosphate within the normal range of less than 4.6 mg/dL, which is an improvement over standard of care.

The most common adverse effect – diarrhea — occurred in 23.3% of treated patients, but only 1.2% discontinued tenapanor.

“These data from the NORMALIZE study are unprecedented in terms of the proportion of patients able to achieve serum phosphorus levels < 4.6mg/dL with foundational use of tenapanor,” Stuart Sprague DO, chief of the Division of Nephrology and Hypertension at Northshore University Health System stated in a 2020 news release from Ardelyx. “This represents an important advancement in the management of hyperphosphatemia for patients on dialysis.”

Disclosure: The tenapanor clinical trials were supported by Ardelyx. Please see the original references for a full list of authors’ disclosures.

References

Rosenbaum DP, Yang Y, Silva A, Hernandez GT, Block GA. A long-term, open label study to evaluate the ability of tenapanor alone or in combination with sevelamer to achieve normal serum phosphorus in patients with CKD on dialysis (NORMALIZE). Presented at the virtual National Kidney Foundation 2021 Spring Clinical Meetings, April 6-10, 2021. Poster 226.

Ardelyx announces positive second data analysis from ongoing NORMALIZE phase 4 study evaluating tenapanor in CKD patients on dialysis [news release]. Ardelyx; June 15, 2020.