Results of Phase 3 study of Ardelyx oral NHE3 inhibitor for effective reduction of serum phosphorus levels announced

Ardelyx recently announced the evaluation of the results of the Phase 3 PHREEDOM study (n=423, 52 weeks) of the long-term monotherapy of the oral sodium-hydrogen exchanger 3 (NHE3) inhibitor tenapanor for the control of serum phosphorus in adult patients with chronic kidney disease (CKD) dialysis It has been published in Kidney360, the journal of the American Society of Nephrology (ASN), with the title of the article: Safety and Efficacy of Tenapanor for Long-term Serum Phosphorus Control in Maintenance Dialysis: A 52-Week Randomized Phase 3 Trial (PHREEDOM)

In July this year, the US FDA issued a complete response letter (CRL) for tenapanor's new drug application (NDA) for CKD dialysis adult patients to control serum phosphorus levels (treatment of hyperphosphatemia)

PHREEDOM is one of three phase 3 clinical trials supporting NDA, which is a 52-week randomized phase 3 study of monotherapy

Tenapanor chemical structure (picture source: pharmawiki.

Reducing serum phosphorus is the primary task of managing dialysis patients

Tenapanor was discovered and developed by Ardelyx.

In December 2017, Fosun Pharma obtained the exclusive development and commercialization license of tenapanor in China (including Mainland China, Hong Kong and Macau Special Administrative Regions) from Ardelyx

In the treatment of IBS-C, tenapanor reduces the absorption of sodium by the small intestine and colon by inhibiting NHE3 on the top surface of intestinal epithelial cells, which leads to an increase in the secretion of water into the intestinal lumen, thereby accelerating intestinal peristalsis and making stool softer and looser.

In the United States, in September 2020, tenapanor (trade name: Ibsrela, 50mg tablets) was approved by the FDA.

tenapanor mechanism of action

In the treatment of hyperphosphatemia in CKD dialysis patients, since the function of NHE3 is to exchange protons (H+) and absorb sodium (Na+), tenapanor inhibits NHE3 on the top surface of intestinal epithelial cells and increases intracellular protons (H+).

Ardelyx has carried out 3 phase 3 clinical trials to evaluate the efficacy and safety of tenapanor in controlling serum phosphorus in adult patients with CKD dialysis: (1) 2 monotherapy trials-short-term monotherapy phase 3 BLOCK study (n =219, 12 weeks), long-term single-agent therapy Phase 3 PHREEDOM study (n=423, 52 weeks); (2) 1 dual mechanism trial-Phase 3 AMPLIFY study (n=235, 4 weeks), evaluating tenapanor combination The dual-mechanism therapy of phosphate binders is compared with single-use phosphate binders

All three phase 3 trials reached the primary and key secondary endpoints: tenapanor, short-term, long-term, and combination with phosphate binders significantly reduced serum phosphorus levels

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Original source: Ardelyx Announces Publication of 52-Week Phase 3 PHREEDOM Trial