Last week, at the American Society of Nephrology’s Kidney Week annual meeting, Ardelyx and Kyowa announced additional positive results from their Phase III (PHREEDOM, BLOCK, and AMPLIFY) and Phase II studies, respectively, which investigated the efficacy, safety, and tolerability associated with tenapanor therapy for hyperphosphatemia (HP) in chronic kidney disease (CKD) patients who are on dialysis. GlobalData still expects tenapanor to gain a front-line position in the CKD-HP market due both to its novel mechanism of action and its opportunity to address two long-standing unmet needs. Tenapanor monotherapy would help improve patient compliance by reducing pill burden, and combination therapy would provide a dual mechanism approach in treating refractory CKD-HP patients.
An analysis of the Phase III PHREEDOM study showed that tenapanor proved to be both efficacious and safe. Specifically, it found that tenapanor treatment resulted in sustained reductions in serum phosphorus concentrations and a decrease in mean serum phosphorus, from 7.7mg/dL to 5.1mg/dL. Analyses of the BLOCK and AMPLIFY Phase III trials showed that tenapanor was efficacious both when administered as a monotherapy or when used with phosphate binders in treating refractory HP patients. Additionally, analyses of the PHREEDOM, BLOCK, and AMPLIFY trials showed that tenapanor was well tolerated across the studies.
Similar results were achieved in Phase II studies in Japan, and a mean serum phosphorus decrease of 2.6mg/dL was observed with tenapanor monotherapy. In a refractory HP population, Phase II studies in Japan showed that tenapanor treatment conferred a mean serum phosphorus decrease of 2.1mg/dL when used with phosphate binders.
Tenapanor is an inhibitor of sodium/hydrogen exchanger isoform 3 (NHE3), which is found in the kidneys and acts to regulate sodium absorption and secretion in the body under normal physiological conditions. This reduces the intestinal absorption of both dietary sodium and phosphorus, making it a viable agent to address CKD-HP, including refractory patients. In a monotherapy setting, 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 with each meal. Unlike most marketed phosphate binders, tenapanor aims to reduce this pill burden, 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 entered a licensing agreement with Kyowa Hakko Kirin. Ardelyx submitted a New Drug Application to the FDA for tenapanor in June 2020 for the treatment of HP in CKD patients on dialysis.