The FDA's rejection of Ardelyx’s chronic kidney disease prospect last summer drew a rebuke from the company and analysts. But as an FDA panel of outside experts gathers to re-assess the drug on Wednesday, it appears Ardelyx and the agency may lock horns yet again.
In briefing documents published Monday, staff reviewers from the FDA’s cardiology and nephrology division questioned the overall efficacy of Ardelyx’s NHE3 inhibitor tenapanor, which debuted in irritable bowel syndrome in April under the brand name Ibsrela.
In chronic kidney disease (CKD), tenapanor works by reducing serum phosphorus, which often builds up in CKD patients in a condition known as hyperphosphatemia. In certain patients, high phosphate levels can cause blood calcium levels to drop, potentially leading to muscle cramps or spasms, rashes, bone and joint pain, and more.
Currently, phosphate binders are the only approved therapy for hyperphosphatemia.
Still, the problem with Ardelyx's application is that tenapanor’s “magnitude of treatment effect appears less than that observed with approved drugs,” FDA staffers said in the new briefing documents.
In Ardelyx’s complete response letter last summer, the regulator admitted Ardelyx’s data offered “substantial evidence” that tenapanor reduces serum phosphorous in CKD patients on dialysis. But the FDA noted the treatment effect was “small and of unclear clinical significance,” putting Ardelyx on the hook to run another study before it could reapply for approval.
“We do not agree with the FDA's subjective assessment on the clinical relevance of the treatment effect of tenapanor,” Mike Raab, president and CEO of Ardelyx, said in a statement last year.
Some analysts agreed, with a team at Piper Sandler saying at the time it was “flummoxed" by the FDA’s “conflicting messaging” around the med’s application.
Ardelyx faced another rejection in February after it appealed the CRL, but even still, the company refused to back down.
Ultimately, Ardelyx’s persistence paid off as the company in April scored a review before the FDA’s Cardiovascular and Renal Drug Advisory Committee. This week, outside experts are set to weigh in on the application.
While the FDA appears to be sticking to its guns on tenapanor’s CKD rejection, the concerns raised Monday shouldn’t come as a surprise, Citi analysts said, as reported by Reuters. The analysts argued that the documents set the tone for a positive discussion when the committee meets on Wednesday.
Regardless of the meeting’s outcome, Ardelyx seems determined to stay the course in CKD.
While the company didn’t immediately respond to Fierce Pharma’s request for comment, Ardelyx CEO Mike Raab told Biospace “[t]he nephrology community has spoken loudly and clearly that they want innovation for chronic kidney disease patients on dialysis,” adding that his company is “committed to finding a path forward for [tenapanor].”