Fosun Pharma has received approval from China's National Medical Products Administration (NMPA) for Wan Ti Le (tenapanor hydrochloride tablets), bringing a novel phosphate management option to dialysis patients with hyperphosphatemia. The drug is specifically indicated for controlling serum phosphorus levels in dialysis patients with chronic kidney disease (CKD) who have an inadequate response or are intolerant to phosphorus binders.
Tenapanor represents a significant advancement in hyperphosphatemia treatment as the world's first and currently only approved phosphate absorption inhibitor. This approval introduces a new mechanism of action to the Chinese market for managing a condition that has historically been difficult to control with existing therapies.
"The approval of tenapanor for the treatment of adult dialysis patients with chronic kidney disease in China market brings new hope for dialysis patients with hyperphosphatemia in China," said Xingli Wang, Executive President and CEO of Global R&D Center of Fosun Pharma. "Fosun Pharma is committed to addressing unmet clinical needs by focusing on innovative R&D in core therapeutic areas such as oncology, immunology, and chronic diseases."
Mike Raab, president and chief executive officer of Ardelyx, which licensed the drug to Fosun Pharma Industrial, added: "The approval of tenapanor for hyperphosphatemia in China marks another important milestone in Ardelyx's commitment to bringing our novel therapies to patients with unmet medical needs globally."
Addressing a Significant Unmet Need
Hyperphosphatemia management remains challenging in China's dialysis population. By the end of 2023, China had more than one million patients on maintenance hemodialysis, with an annual growth rate of approximately 10%. Among these patients, 76% have hyperphosphatemia, yet only 39% achieve target phosphate levels according to China's hemodialysis quality control standards (serum phosphate 1.13-1.78 mmol/L).
The situation is even more concerning when measured against the stricter Chinese guidelines for the diagnosis and treatment of Chronic Kidney Disease Mineral and Bone Disorder (CKD-MBD), which set the target range for serum phosphate at 0.87-1.45 mmol/L. Under these guidelines, the achievement rate drops to just 26.7%.
Recognizing this challenge, the National Health Commission of China has listed "improving phosphate control rates in hemodialysis patients" as a key quality control improvement target for 2024.
Novel Mechanism of Action
Tenapanor works differently from traditional phosphate binders. It is a local inhibitor that targets the sodium/hydrogen exchanger-3 (NHE3), a reverse transporter expressed on the apical surface of the epithelium in the small intestine and colon.
By inhibiting NHE3, tenapanor tightens intercellular junctions, reducing the permeability of the paracellular pathway to phosphate—the primary route for intestinal phosphate absorption. This mechanism leads to decreased phosphate absorption and consequently reduces serum phosphorus levels.
Proven Clinical Efficacy
The drug's efficacy has been demonstrated in multiple clinical studies. In a randomized, double-blind, placebo-controlled study involving 164 hemodialysis patients with hyperphosphatemia, eight weeks of treatment with tenapanor in combination with phosphate binders decreased serum phosphate levels by an additional 0.57 mmol/L compared to phosphate binders alone.
Another multicenter, randomized, open-label study enrolled 303 hemodialysis patients who were not achieving target phosphate levels with phosphate binders. After switching to a tenapanor-based regimen (tenapanor 30 mg twice daily, with phosphate binders added or adjusted if necessary), the rate of achieving target phosphate levels increased by 34.4% to 38.2% after 10 weeks of treatment.
Beyond phosphate control, tenapanor can lower levels of parathyroid hormone (PTH) and fibroblast growth factor 23 (FGF23), aiding in the comprehensive management of CKD-mineral and bone disorder.
Regulatory Status
Tenapanor hydrochloride tablets is a first-in-class oral intestinal sodium/hydrogen exchanger 3 inhibitor licensed by Fosun Pharma Industrial from Ardelyx, Inc. The drug received approval from the U.S. Food and Drug Administration in October 2023 to reduce serum phosphorus in adults with CKD on dialysis as add-on therapy in patients who have an inadequate response to phosphate binders or who are intolerant of any dose of phosphate binder therapy.
The drug is also approved for the treatment of Irritable Bowel Syndrome with Constipation in the U.S. and Hong Kong SAR.
Future Outlook
The approval of tenapanor in China represents a significant advancement in the management of hyperphosphatemia in dialysis patients. By offering a complementary mechanism to existing phosphate binders, tenapanor provides clinicians with a new tool to improve phosphate control rates and potentially reduce the complications associated with hyperphosphatemia.
Both Fosun Pharma and Ardelyx have expressed their commitment to continued collaboration in bringing innovative therapies to patients with unmet medical needs. As tenapanor becomes available to patients in China, it may help address the National Health Commission's goal of improving phosphate control rates in hemodialysis patients.
