FDA Briefing Documents Cast Doubt on Ardelyx’s CKD Drug (Updated)

FDA_Sarah Silbiger/Getty Images

Sarah Silbiger/Getty Images

The FDA raised doubts Monday about the future of Ardelyx's experimental chronic kidney disease drug tenapanor in briefing documents released ahead of a Wednesday advisory committee meeting.

The regulator highlighted concerns about the overall efficacy of the medication.

In its briefing documents, the FDA suggested that the “magnitude of treatment effect” is lower than that with approved medications for the control of serum phosphorus in adult patients with CKD who are on dialysis.

On Wednesday, the FDA’s Cardiovascular and Renal Drugs Advisory Committee will hold a meeting to evaluate the New Drug Application for tenapanor, a sodium hydrogen exchanger 3 inhibitor designed to control serum phosphorus by inhibiting the sodium hydrogen exchanger 3.

This is the second time tenapanor has come up in front of the FDA. Last year, the regulatory agency issued a Complete Response Letter for the drug candidate despite the candidate hitting its primary endpoint in late-stage studies.

The clinical data showed tenapanor reduces serum phosphorus in CKD patients on dialysis but at the time of the CRL, the regulator called the results “small and of unclear clinical significance.”

Monday's briefing documents suggest scientists with the regulatory agency may be leaning that way again. The review team suggested the efficacious data seen in tenapanor clinical programs may not provide a significant improvement over the current standard of care, which is phosphate binders.

“We expect that tenapanor’s average treatment effect on s-P (serum phosphate) when used in patients who tolerate and remain on therapy is about 0.7 mg/dL. The magnitude of the treatment effect appears to be less than that observed with approved agents,” the reviewers wrote.

When the committee meets Wednesday, the members will not only evaluate the available clinical data from tenapanor’s trials but nephrologists and experts in treating dialysis patients, including those who cannot control serum phosphorous levels, will provide their input.

Mike Raab, president and chief executive officer of Ardelyx, told BioSpace the company is looking forward to a robust discussion with the advisory committee.

“The nephrology community has spoken loudly and clearly that they want innovation for chronic kidney disease patients on dialysis and at Ardelyx we are committed to finding a path forward for [tenapanor],” he said. 

Although the FDA previously rejected tenapanor, Ardelyx has been adamant about the potential of the medication for these patients. The company has continued to push for potential approval of the drug in this indication, which has a high unmet need.

An inability to control serum phosphate levels is called hyperphosphatemia. It leads to leaching of the calcium in the bones. That causes the bones to become weak and leads to the leached calcium forming deposits in other parts of the body.

Earlier this month, BioSpace spoke with some nephrologists about the seriousness of the condition. Patients who cannot control serum phosphorous levels are required to maintain a strict diet that includes phosphate binders taken with each meal. Patients typically take between 10 and 20 phosphate binders per day, depending on how many times they eat.

Dr. Jay Wish, professor of clinical medicine at Indiana University School of Medicine and chief medical officer for outpatient dialysis at Indiana University Health, said beyond the pill burden, side effects of phosphorous binders include bloating and constipation. One side effect of tenapanor is potential diarrhea, which he said might provide some welcome relief to these patients.

Tenapanor was previously approved by the FDA as a treatment for irritable bowel disease with constipation.  

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