Earlier this month, Ardelyx announced positive results from its Phase III PHREEDOM study, which investigated the efficacy and safety associated with tenapanor monotherapy in chronic kidney disease (CKD)-induced hyperphosphatemia (HPT) patients who are dialysis-dependent.
The drug boasts a novel mechanism of action via the phosphorus absorption pathway and also aims to improve patient compliance by reducing the notorious pill burden associated with the current standard of care. GlobalData believes that tenapanor will gain a front-line position in the HPT market due to its mechanistic edge against the dated phosphate binder therapeutics and through addressing long-standing HPT treatment compliance issues.
In the Phase III PHREEDOM trial, 564 patients were assessed in a randomized study, either treated with tenapanor for 26 weeks or treated with sevelamer for 52 weeks. Tenapanor-treated patients were randomized further, either continuing treatment with tenapanor or switching to placebo, for a withdrawal period. Tenapanor met its primary endpoint by demonstrating a statistically significant difference compared to placebo in least square mean serum phosphorus change (-1.4 mg/dL, p<0.0001). It is also important to note that 77% of patients given tenapanor in the 26-week treatment period experienced a decrease in serum phosphorus. During the same treatment period, 17.2% of tenapanor-treated patients had a serious adverse event (AE) versus 22.6% of sevelamer-treated patients. The most common AE was diarrhoea.
Tenapanor is an inhibitor of sodium/hydrogen exchanger isoform 3 (NHE3) found in the kidneys, which acts to regulate sodium absorption and secretion in the body under normal physiological conditions. Orally administered tenapanor has been shown to reduce the intestinal absorption of both dietary sodium and phosphorus, making it a viable agent to address HPT in CKD patients. The limited binding efficacy of various marketed phosphate binders has led to the requirement for patients to ingest a large number of tablets or capsules per day. Phosphate binder tablets must be taken with each meal, the number of which can be anywhere from 6 – 12 tablets per day. Unlike most marketed phosphate binders, tenapanor will significantly reduce this pill burden as it is administered twice daily, thereby boosting patient compliance.
Ardelyx is a biopharmaceutical company headquartered in California, US, which originally entered into a marketing partnership with AstraZeneca in 2012 to commercialize tenapanor. However, Ardelyx announced that it had entered into a termination agreement with AstraZeneca in 2015, returning the marketing rights of tenapanor to Ardelyx. In Japan, Ardelyx is developing tenapanor with its collaboration partner, Kyowa Hakko Kirin. Ardelyx plans to submit a New Drug Application to the FDA for tenapanor in mid-2020 for the treatment of CKD-induced HPT in dialysis patients. The drug was already approved by the FDA for the treatment of patients with irritable bowel syndrome with constipation in September of this year.
GlobalData (2020) Chronic Kidney Disease-Induced Anemia – Opportunity Analysis and Forecasts to 2029, to be published.
GlobalData (2019) Chronic Kidney Disease–Mineral Bone Disorders (CKD-MBD): Competitive Landscape to 2027, March 2019, GDHC023CL.
GlobalData (2017) OpportunityAnalyzer: Late-Stage Chronic Kidney Disease – Opportunity Analysis and Forecasts to 2026, December 2017, GDHC082POA.