Ardelyx's Regulatory Battle Continues as FDA Denies Appeal


FDA_Sarah Silbiger/Getty Images

Sarah Silbiger/Getty Images

Ardelyx reported in a regulatory filing that the U.S. Food and Drug Administration sent an Appeal Denied Letter (ADL) for its drug tenapanor, a therapeutic intended for chronic kidney disease.

The ADL comes after the company submitted a formal dispute resolution request in December 2021, following the FDA’s complete response letter (CRL) asking Ardelyx to conduct additional trials.

The battle between Ardelyx and the FDA over tenapanor began in July 2021 after the company submitted a new drug application to the FDA. Tenapanor met all primary and secondary endpoints in Phase III trials, including patient safety and tolerance. However, the FDA denied approval, stating that although clinical data provided evidence of efficacy, the breadth of efficacy was small and of unclear clinical significance. The rejection also came after the FDA sent a letter to Ardelyx, stating it had found deficiencies that warranted a discussion of labeling and post-marketing requirements.

The FDA told Ardelyx that it would need to conduct an additional adequate and well-controlled trial demonstrating clinically relevant treatment effect to continue the approval process. Instead, Ardelyx submitted a formal dispute resolution request, a decision that came after it was unable to achieve resolution with the FDA during an End of Review meeting. Such a request allowed the company to raise scientific disagreement above the division level within the FDA’s Division of Cardiology and Nephrology.

In its ADL, the FDA provided Ardelyx with an additional path forward for resubmitting the new drug approval without conducting a further trial. This path would involve several new analyses from Phase III data, an assessment of tenapanor’s benefits and risks, and a proposal to label the drug for providers. Ardelyx intends to appeal the ADL to the Office of New Drugs, Center for Drug Evaluation and Research. If the appeal is accepted for consideration, the company expects to hear a decision in April 2022.

In Nov. 2021, Ardelyx presented numerous positive results from its trials using tenanapor at the American Society of Nephrology Kidney Week. The company provided results that showed tenapanor was able to selectively decrease serum phosphorous by inhibiting paracellular phosphate absorption without impacting other serum electrolytes of albumin, a primary treatment target in chronic kidney disease as high phosphorus levels can cause damage within the body. The company also presented patient-reported data that indicated that patients treated with the drug experienced improved treatment experience.

 “As a person living with kidney disease who has struggled with managing phosphorus, it gives me great hope to see the patient perspective and patient priorities being incorporated into clinical studies,” said Derek Forfang, chair, NKF Kidney Patient Advocacy Committee and co-chair, Forum of ESRD Networks’ Kidney Patient Advisory Council in regard to positive data presented. “The OPTIMIZE results suggest that tenapanor could have an enormous positive impact on the health and quality of life of many patients on dialysis through its novel mechanism that blocks, not binds, phosphorus. Tenapanor has the potential to help more patients achieve target phosphorus levels and reduce the treatment burden associated with currently available hyperphosphatemia therapies. The incorporation of the patient voice into the clinical trial design and evaluation of tenapanor is a huge step forward for patients.”

Patients will be eager to see what comes next for tenapanor.                 

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