title: VS-501: A NOVEL, NON-ABSORBED, CALCIUM- AND ALUMINUM-FREE, HIGHLY EFFECTIVE PHOSPHATE BINDER DERIVED FROM NATURAL PLANT POLYMER.
abstract: Inadequate control of serum phosphate in chronic kidney disease can lead to pathologies of clinical importance. Effectiveness of on-market phosphate binders is limited by safety concerns and low compliance due to high pill size/burden and gastrointestinal discomfort. VS-501 is a non-absorbed, calcium- and aluminum-free, chemically-modified, plant-derived polymer. In vitro studies show that VS-501 has a high density and a low swell volume when exposed to simulated gastric fluid (vs. sevelamer). When male Sprague Dawley (SD) rats on normal diet were treated with VS-501 or sevelamer, serum phosphate was not significantly altered, but urinary phosphate levels decreased by >90%. VS-501 had no effect on serum calcium (Ca) or urinary Ca, while 3% sevelamer significantly increased serum and urine Ca. In 5/6 nephrectomized (NX) uremic SD rats on high-phosphate diet, increasing dietary phosphate led to an increase in serum and urine phosphate, which was prevented in rats treated with VS-501 or sevelamer (0.2-5% in food). High phosphate diet also increased serum FGF-23 and parathyroid hormone in 5/6 NX rats, which was prevented by VS-501 or sevelamer. VS-501 or sevelamer increased fecal phosphate in a dose-dependent manner. More aortic calcification was observed in 5/6 NX rats treated with 5% sevelamer, while VS-501 and sevelamer did not show significant effects on cardiac parameters, fibrosis, intestine histology and intestinal sodium-dependent phosphate cotransporter gene expression. These results suggest that VS-501 is effective in binding phosphate with no effects on calcium homeostasis, and may have improved pill burden and gastrointestinal side effects.
authors.affiliation: Vidasym, Chicago, IL.
authors.forename: J Ruth
authors.initials: JR
authors.lastname: Wu-Wong
authors.affiliation: Vidasym, Chicago, IL.
authors.forename: Yung-Wu
authors.initials: YW
authors.lastname: Chen
authors.affiliation: University of Illinois, Chicago, IL.
authors.forename: Robert
authors.initials: R
authors.lastname: Gaffin
authors.affiliation: University of Illinois, Chicago, IL.
authors.forename: Andy
authors.initials: A
authors.lastname: Hall
authors.affiliation: Vidasym, Chicago, IL.
authors.forename: Jonathan T
authors.initials: JT
authors.lastname: Wong
authors.affiliation: Vidasym, Chicago, IL.
authors.forename: Joseph
authors.initials: J
authors.lastname: Xiong
authors.affiliation: Vidasym, Chicago, IL.
authors.forename: Jerry L
authors.initials: JL
authors.lastname: Wessale
keywords: Chronic kidney disease; Hyperphosphatemia; Phosphate; Phosphate binder; Phosphorus; VS-501