On 7 June, at the European Renal Association–European Dialysis and Transplant Association congress, Ardelyx presented in two sessions highlighting interim data from the ongoing OPTIMIZE study. GlobalData still expects tenapanor to gain a frontline position in the chronic kidney disease–hyperphosphataemia (CKD-HP) market due both to its novel mechanism of action and its opportunity to address two long-standing unmet needs. Tenapanor monotherapy has the potential to improve patient compliance by reducing pill burden, and combination therapy would provide a dual-mechanism approach in treating refractory CKD-HP patients.
Key opinion leaders (KOLs) interviewed by GlobalData have emphasised tenapanor’s potential to be an alternative therapy option to traditional phosphate binders, such as sevelamer, while also offering a smaller pill size and not requiring mealtime administration. Despite the advantageous clinical data on tenapanor, the drug is expected to enter the mature dialysis market and will likely face notable barriers in entry against marketed iron-based binders, Velphoro (sucroferric oxyhydroxide) and Auryxia (ferric citrate), as well as the dominant cheaper calcium-based binders and sevelamer.
The primary endpoint of the Phase IV OPTIMIZE is to evaluate the use of tenapanor as the main therapy option for CKD-HP patients on dialysis. Interim data from the company’s ongoing OPTIMIZE study show that tenapanor achieved greater phosphorus targets in binder-treated patients with phosphorus greater than 5.5mmol/L. Tenapanor can also help control serum phosphorus in binder-naïve patients. Analyses of the Phase III PHREEDOM study showed that patients on tenapanor had a smaller percentage of deaths and hospitalisations compared to patients on the phosphate binder sevelamer.
Despite these results, some US-based KOLs have stated that, in general, monotherapy for treating high phosphate does not work and that, therefore, tenapanor will likely have to be integrated into existing HP treatment paradigms. KOLs further emphasised that if tenapanor is approved, a prior authorisation might be put in place in prescription plans and so patients would have to have failed a traditional guideline-recommended therapy in order to get it.
Tenapanor is an inhibitor of the sodium/hydrogen exchanger isoform III found in the kidneys, which acts to regulate sodium absorption and secretion in the body under normal physiological conditions. Ardelyx is a biopharmaceutical company headquartered in California that originally entered into a marketing partnership with AstraZeneca in 2012 to commercialise tenapanor. Ardelyx announced, however, 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 for the development and commercialisation of tenapanor for HP. In China, Ardelyx entered a licensing agreement with Shanghai Fosun Pharmaceutical Industrial Development Company Limited for the development and commercialisation of tenapanor for CKD-HP. In Canada, Ardelyx entered a licensing agreement with Knight Therapeutics for the commercialisation of tenapanor for HP. Ardelyx’s new drug application for tenapanor is currently under review by the US Food and Drug Administration (FDA), with a Prescription Drug User Fee Act date of 29 July.