FDA committee votes in favor of Xphozah for phosphate control in patients on dialysis
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An FDA advisory committee voted 9-4 in favor of the use of Xphozah as a monotherapy for controlling serum phosphorus levels in adults with chronic kidney disease on dialysis.
Members of the Cardiovascular and Renal Drugs Advisory Committee (CRDAC) also voted 10-2 (with one abstention) in favor of using Xphozah (tenapanor, Ardelyx Inc.) in combination with phosphate binders.
“I think there is a benefit for some patients to use this as monotherapy, particularly those who don’t want to take other products for phosphorus control,” Julia B. Lewis, MD, professor of medicine in the division of nephrology at Vanderbilt Medical Center and CRDAC chair, said in explaining her vote. She acknowledged that “larger clinical trials with active comparators” should be conducted to show clinical benefit. “Demonstrating a benefit is important because of the side effects,” she said.
In Ardelyx’s three phase 3 clinical trials evaluating the safety and efficacy of tenapanor – Phreedom, Block and Amplify – mild to severe cases of diarrhea were common in patients who took the drug, company officials said at the hearing.
If approved by the FDA, the drug will be the first and only phosphate absorption inhibitor, reducing serum phosphorus with one pill taken twice daily, according to a company press release. The agency has 30 days to review tenapanor, according to the release.
“Today’s vote by the CRDAC is a promising development for the chronic kidney disease community, as patients continue to struggle to control serum phosphorus levels despite use of currently available therapies, which are all limited to the phosphate binder class,” Mike Raab, president and CEO of Ardelyx, said in the release.
“Xphozah is a novel treatment that provides a clinically meaningful effect on serum phosphate,” Sharon Moe, MD, chief of the division of nephrology and hypertension at Indiana University School of Medicine, said. “I am encouraged by the committee’s vote. The nephrology community is enthusiastic to have access to this therapy with its novel mechanism of action to help our patients.”
FDA review
The FDA accepted Ardelyx’s new drug application for the drug in September 2020 with a Prescription Drug User Fee Act goal date of April 29, 2021. After a 3-month delay, the agency turned down the drug for approval in July 2021. In a press release, the company said the FDA’s complete response letter indicated that while it agreed that “the submitted data provide substantial evidence that tenapanor is effective in reducing serum phosphorus in CKD patients on dialysis,” the company said the agency characterized the magnitude of the treatment effect as “small and of unclear clinical significance.”
Ardelyx said in the release at the time that the FDA wanted the company “to conduct an additional adequate and well-controlled trial demonstrating a clinically relevant treatment effect on serum phosphorus or an effect on the clinical outcome thought to be caused by hyperphosphatemia in CKD patients on dialysis.”
After meeting with the FDA, Ardelyx received approval to have the drug reviewed by the CRDAC.
Ardelyx received approval from the FDA in September 2019 for Ibsrela (tenapanor) for the treatment of irritable bowel syndrome with constipation.
Benefits and risks
CRDAC members were charged by the FDA to determine whether benefits of the drug outweigh its risks for the control of serum phosphorus in adults when administered as monotherapy and whether benefits of the drug outweigh its risks for the control of serum phosphorus when administered in combination with phosphate binder treatment.
Ardelyx executives and medical staff, as well as FDA investigators reviewing the benefits and outcomes of the drug, provided testimony at the hearing. During the open forum period, patients testified that current phosphate binders carry a large daily pill burden and have adverse events, like constipation.
“I have to take 12 ‘horse pills’ a day,” Dawn Edwards, a patient on hemodialysis, told the committee, “and I am fluid restricted because of my kidney failure. Taking over five pills a meal is overwhelming ... think of us as you make your decision today.”
“Phosphate binders make up over half of the pill burden for patients,” Glenn M. Chertow, MD, MPH, chief of the division of nephrology at Stanford University School of Medicine, said in testimony on behalf of Ardelyx. “Current phosphate binders are inadequate ... we need more options” to control and manage hyperphosphatemia, he said. “We need fewer pills, smaller pills and less dosing. In my view, the demonstrated benefits are clinically meaningful and could improve management.”
References:
Ardelyx announces FDA Advisory Committee votes that the benefits of Xphozah (tenapanor) outweigh its risks for the control of serum phosphorus in adult patients with chronic kidney disease on dialysis. https://ir.ardelyx.com/news-releases/news-release-details/ardelyx-announces-fda-advisory-committee-votes-benefits-xphozahr. Published Nov. 17, 2022. Accessed Nov. 17, 2022.
Ardelyx receives complete response letter from U.S. FDA for new drug application for tenapanor for the control of serum phosphorus in adult patients with CKD on dialysis. https://ir.ardelyx.com/news-releases/news-release-details/ardelyx-receives-complete-response-letter-us-fda-new-drug. Published July 29, 2021. Accessed Nov. 17, 2022.
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