The FDA has issued an Appeal Denied Letter (ADL) to Ardelyx concerning tenapanor for chronic kidney disease (CKD)-hyperphosphatemia (HP). The ADL comes after Ardelyx submitted a formal dispute resolution request in December 2021. In July 2021, the FDA issued a Complete Response Letter (CRL) to Ardelyx concerning tenapanor’s New Drug Application (NDA) for CKD-HP. The response letter stated that Ardelyx was required to conduct an additional clinical study to show the clinically significant effect of tenapanor on serum phosphorus in CKD-HP.
Following the CRL, Ardelyx laid off 65% of its employees and filed a formal dispute resolution request with the FDA’s division of Cardiology and Nephrology. Ardelyx is looking to appeal the ADL to the Office of New Drugs to review the matter. If approved, tenapanor is expected to enter the mature dialysis market, and will likely face notable barriers in entry against marketed iron-based binders, Vifor Pharma ’s Velphoro (sucroferric oxyhydroxide) and Akebia Therapeutics ’s Auryxia (ferric citrate), as well as the dominant cheaper calcium-based binders and sevelamer.
The Office of New Drugs is expected to respond to the latest appeal in April 2022. If the appeal is successful, Ardelyx may refile for approval without conducting further trials. Tenapanor has the potential to capture a slice of the HP market by targeting dialysis-dependent patients who are not able to maintain recommended phosphate levels despite undergoing treatment and adhering to restrictions on dietary phosphate intake. If approved, GlobalData expects tenapanor to gain a frontline 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 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.
Key opinion leaders interviewed by GlobalData emphasized that when it comes to CKD-HP, nephrologists want patients to reach a target serum phosphorous level of 2.5–4.5mg/dL. An analyses of the Phase III PHREEDOM study showed that patients who received tenapanor had a smaller percentage of deaths and hospitalizations compared to patients on the phosphate binder sevelamer. Specifically, the analysis 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.
Tenapanor is an inhibitor of the sodium/hydrogen exchanger isoform 3 found in the kidneys, which acts to regulate sodium absorption and secretion in the body under normal physiological conditions.