The FDA approved the first-in-class phosphate absorption inhibitor tenapanor (Xphozah) to reduce serum phosphorus in chronic kidney disease (CKD) patients on dialysis, developer Ardelyx announced on Tuesday.
An oral drug, tenapanor is specifically indicated as an add-on therapy for adult patients with an inadequate response to phosphate binders or for those who are intolerant of the drugs, and marks the first new treatment option for CKD patients on dialysis with hyperphosphatemia in over 3 decades.
Underpinning the agency’s decision were three phase III trials — PHREEDOM, BLOCK, and AMPLIFY — that tested tenapanor as monotherapy and in combination with binder therapy; each met their primary and key secondary endpoints.
“Hyperphosphatemia management has been a persistent clinical challenge, as the majority of patients receiving maintenance dialysis are unable to consistently achieve target serum phosphate concentrations despite treatment with phosphate binders,” study investigator Glenn Chertow, MD, MPH, of Stanford University in California, said in a statement.
“In patients not adequately responding to phosphate binder therapy, Xphozah has been shown to help increase the proportion of patients achieving target serum phosphate concentrations,” Chertow added. “I believe Xphozah can advance the care of patients with hyperphosphatemia, providing a new treatment option with a complementary mechanism of action.”
Tenapanor acts locally in the gut to inhibit the sodium hydrogen exchanger 3 (NHE3) to reduce phosphate absorption through the paracellular pathway, the primary pathway of phosphate absorption.
The biggest treatment effect was noted in the PHREEDOM trial, with an estimated mean change in serum phosphate level between tenapanor and placebo of -1.4 mg/dL (P<0.0001) from the beginning to the end of the randomized withdrawal period.
Despite meeting its endpoints in the phase III trial program, the path to approval for tenapanor in CKD was not entirely smooth, with FDA rejecting the drug in 2021, at the time calling the drug’s effect “small and of unclear clinical significance.” But fortunes for the phosphate absorption inhibitor changed after an FDA advisory committee recommended approval by a vote of 9-4 last November.
As far as safety, diarrhea was the only adverse event reported in at least 5% of patients, which occurred in up to 53% of patients; cases were mostly mild-to-moderate but the label warns that patents may experience severe diarrhea.
Tenapanor is recommended at a 30-mg dose, with the tablet taken twice daily before morning and evening meals. It’s contraindicated in patients under 6 years of age and in those with known or suspected mechanical gastrointestinal obstruction. The label suggests monitoring serum phosphorus and to adjust the dosage as needed to manage gastrointestinal tolerability (it also comes in 10 mg and 20 mg tablets).
Tenapanor for CKD is expected to be available in November. The drug is also approved under the brand name Ibsrela for irritable bowel syndrome with constipation.