Efficacy, tolerability, and safety of the oral phosphate binder VS-505 (AP301).

Abstract

BACKGROUND:

VS-505 (AP301), an acacia and ferric oxyhydroxide polymer, is a novel fiber-iron-based phosphate binder. This two-part phase 2 study evaluated the tolerability, safety, and efficacy of oral VS-505 administered three times daily with meals in treating hyperphosphatemia in chronic kidney disease (CKD) patients receiving maintenance hemodialysis (MHD).

METHODS:

In Part 1, patients received dose-escalated treatment with VS-505 2.25, 4.50, and 9.00 g/day for 2 weeks each, guided by serum phosphorus levels. In Part 2, patients received randomized, open-label, fixed-dosage treatment with VS-505 (1.50, 2.25, 4.50, or 6.75 g/day) or sevelamer carbonate 4.80 g/day for 6 weeks. The primary efficacy endpoint was the change in serum phosphorus.

RESULTS:

The study enrolled 158 patients (Part 1: 25; Part 2: 133), with 130 exposed to VS-505 in total. VS-505 was well tolerated. The most common adverse events were gastrointestinal disorders, mainly feces discolored (56%) and diarrhea (15%; generally during weeks 1‒2 of treatment). Most gastrointestinal disorders resolved without intervention, and none were serious. In Part 1, serum phosphorus significantly improved (mean change -2.0 mg/dL; 95% confidence interval -2.7, -1.4) after VS-505 dose escalation. In Part 2, serum phosphorus significantly and dose-dependently improved in all VS-505 arms, with clinically meaningful reductions with VS-505 4.50 and 6.75 g/day, and sevelamer carbonate 4.80 g/day (mean change -1.6 (-2.2, -1.0), -1.8 (-2.4, -1.2), and -1.4 (-2.2, -0.5) mg/dL, respectively). In both Parts, serum phosphorus reductions occurred within 1 week of VS-505 initiation, returning to baseline within 2 weeks of VS-505 discontinuation.

CONCLUSION:

VS-505, a novel phosphate binder, was well tolerated with a manageable safety profile, and effectively and dose-dependently reduced serum phosphorus in CKD patients with hyperphosphatemia receiving MHD. Clinical Trial registration number: NCT04551300.

• Authors: Bing Zhuang, Liangying Gan, Bin Liu, Weijie Yuan, Ming Shi, Ai Peng, Lihua Wang, Xiaolan Chen, Tongqiang Liu, Shiying Zhang, Song Wang, Qing Gao, Baoxing Wang, Huixiao Zheng, Changhua Liu, Yuan Luo, Hong Ye, Hongli Lin, Yiwen Li, Qiang He, Feng Zheng, Ping Luo, Gang Long, Wei Lu, Kanghui Li, Junwei Yang, Yingxue Cathy Liu, Zhizheng Zhang, Xiaolin Li, Weifeng Zhang, Li Zuo
• Journal: Nephrology, dialysis, transplantation : official publication of the European Dialysis and Transplant Association - European Renal Association (Nephrol Dial Transplant) (Mar 07 2024) ISSN: 1460-2385 [Electronic] England
• PMID: 38453435 (Publication Type: Journal Article)
• Copyright: © The Author(s) 2024. Published by Oxford University Press on behalf of the ERA.