The Food and Drug Administration’s (FDA) Cardiovascular and Renal Drugs Advisory Committee voted in favor (9 to 4) of the use of tenapanor (Xphozah®) as monotherapy for the control of serum phosphorus in adult patients with chronic kidney disease (CKD) on dialysis, as well as its use in combination with phosphate binders (10 to 2, with 1 abstention).

Tenapanor is a first-in-class oral medication designed to block sodium/hydrogen exchanger 3 (NHE3) 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.

During the advisory meeting, the FDA panel reviewed data from three phase 3 trials: PHREEDOM, BLOCK, and AMPLIFY (ClinicalTrials.gov Identifier: NCT03427125, NCT02675998, NCT03824587, respectively) which included more than 1200 adults with CKD on dialysis. The PHREEDOM and BLOCK trials evaluated tenapanor as monotherapy, while the AMPLIFY trial evaluated tenapanor as adjunctive therapy to phosphate binders.

All 3 trials met their primary and key secondary endpoints. For patients who tolerated and remained on therapy, the average treatment effect with tenapanor on serum phosphorus was about -0.7mg/dL, which was less than what has been observed with currently approved therapies.

An analysis of safety data showed no significant safety concerns with tenapanor apart from moderate to severe diarrhea. The committee concluded that there is uncertainty as to whether the impact of diarrhea on tolerability could potentially limit adherence.

Although not bound by the panel’s recommendations, the FDA will take them into consideration when making decisions on Ardelyx’s second level appeal of the Complete Response Letter that was issued last year.

References

  1. Ardelyx announces FDA Advisory Committee votes that the benefits of Xphozah® (tenapanor) outweigh its risks for the control of serum phosphorus in adult patients with chronic kidney disease on dialysis. News release. Ardelyx. Accessed November 17, 2022. https://www.prnewswire.com/news-releases/ardelyx-announces-fda-advisory-committee-votes-that-the-benefits-of-xphozah-tenapanor-outweigh-its-risks-for-the-control-of-serum-phosphorus-in-adult-patients-with-chronic-kidney-disease-on-dialysis-301680780.html.
  2. US Food and Drug Administration. FDA Briefing Document. Drug name: Tenapanor hydrochloride. Accessed November 17, 2022. https://www.fda.gov/media/163150/download.