The US Food and Drug Administration (FDA) recently issued a complete response letter to Ardelyx concerning its New Drug Application (NDA) for tenapanor for the treatment of chronic kidney disease hyperphosphataemia (CKD-HP). The response letter stated that Ardelyx was required to conduct an additional clinical study to show the clinically significant effect of the drug on serum phosphorus in CKD-HP. The NDA consisted of data from three Phase III studies that evaluated tenapanor’s efficacy in more than 1,000 patients.

Despite the FDA’s unexpected response, no concerns were raised regarding tenapanor’s overall safety. The drug has the potential to capture a slice of the HP market by targeting dialysis-dependent patients who cannot maintain recommended phosphate levels despite undergoing treatment and adhering to restrictions on dietary phosphate intake. If eventually approved, GlobalData still expects tenapanor to gain a frontline position in the CKD-HP market due to both its novel mechanism of action and its opportunity to address two long-standing unmet needs. Tenapanor has the potential to be an alternative therapy option to traditional phosphate binders while also offering a smaller pill size and not requiring mealtime administration.

Ardelyx is expected to request a Type A meeting soon to discuss the FDA’s response letter and put together a plan for the approval of tenapanor for the control of serum phosphorus in adult patients with CKD on dialysis. Key opinion leaders interviewed by GlobalData emphasised that when it comes to CKD-HP, nephrologists want patients to reach a target serum phosphorous level of 2.5–4.5mg/dL. 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. Specifically, it found that treatment with tenapanor resulted in sustained reductions in serum phosphorus concentrations and a decrease in mean serum phosphorus from 7.7mg/dL to 5.1mg/dL.

As a result of the FDA’s complete response letter, Ardelyx entered into a sales agreement on 31 August to offer and sell shares of its common stock in a public offering. Ardelyx is looking to use the net earnings from the $150m deal to develop and potentially commercialise tenapanor.

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. In Japan, Ardelyx has entered a licensing agreement with Kyowa Hakko Kirin for the development and commercialisation of tenapanor for HP. In China, Ardelyx has entered a licensing agreement with Shanghai Fosun Pharmaceutical Industrial Development Company for the development and commercialisation of tenapanor for CKD-HP. In Canada, Ardelyx has entered a licensing agreement with Knight Therapeutics for the commercialisation of tenapanor for HP.