Twenty-six million people in America have chronic kidney disease (CKD). Despite the various treatments available to CKD patients, the five-year survival rate is ~33%. Inadequately controlled serum phosphate levels in CKD can lead to various pathologies of clinical importance such as further deterioration of kidney function, cardiovascular complications, renal osteodystrophy, and increased mortality. Current oral phosphate binders on the market have serious shortcomings: (1) suboptimal and inefficient phosphate binding, (2) high pill burden (large number of pills per day), unpalatable and hence low compliance, (3) expensive, especially for the calcium-free phosphate binders, and (4) side effects and safety concerns such as hypercalcemia, aluminum toxication, negative influence on other medication, gastrointestinal (GI) side effects and accumulation in organs. Vidasym has taken a unique approach to discover VS-501, a natural polymer derived from plants that is chemically processed to become highly effective in absorbing phosphate and other minerals in the GI tract without systemic toxicology effects. To confirm VS-501's superior safety and efficacy profiles, an important step is to conduct a head-to-head comparison between VS-501 and sevelamer (the preferred phosphate binder currently on the market) in the clinically validated 5/6 nephrectomized (NX) uremic rat model. Thus, the specific aims of this Phase I study are: (1) to compare the therapeutic efficacy between VS-501 and sevelamer carbonate in the 5/6 NX uremic rats. Acceptance criteria: VS-501 will exhibit better efficacy with less side effects than sevelamer carbonate; (2) to elucidate the renal and cardiovascular benefits of phosphate control in CKD. Acceptance criteria: VS-501 will show better heart and kidney protective effects than sevelamer. Achieving these aims will confirm the superior profile of VS-501 as a clinical candidate to treat hyperphosphatemia in CKD and also demonstrate the efficacy of phosphate control on ameliorating disease progression and cardiovascular complications in CKD, which shall lead to the Phase II IND-enabling studies (safety and toxicology) for VS-501. The completion of Phase II studies will allow VS-501 to enter human clinical trials. Vidasym plans to develop VS-501 into a reimbursable prescription new drug to treat CKD. Once developed, such a drug will not only reduce the mortality rate in CKD, but also reduce the need for dialysis. Current phosphate binders achieve US$1+ billion in annual worldwide sales mainly in dialysis patients. Sevelamer alone showed US$750 million in annual worldwide sales. Estimating from the sales numbers, >90% of dialysis patients receive phosphate binders, but <1% Stage 3/4 CKD patients in US are treated. Assuming VS-501 has a modest 3% penetration into the Stage 3/4/5 CKD patient population (~20 MM patients) at an annual treatment cost of US$2,000 (vs. ~US$3000 for Sevelamer), the estimated annual US sales will be US$1.2 billion. PUBLIC HEALTH RELEVANCE: Vidasym's phase I SBIR study will investigate the feasibility of using Vida-501, Vidasym's novel phosphate binder, to treat hyperphosphatemia and to improve renal and cardiovascular functions in chronic kidney disease (CKD). Globally > 350 million individuals have CKD and this number is projected to increase to >550 million by 2025. Although various modalities and substances are available for CKD, the mortality rate for CKD patients remains high (~33%) and the number of dialysis CKD patients keeps increasing. There is an urgent medical need for the development of an effective and novel resuscitation approach for the treatment of CKD. Hyperphosphatemia in CKD is linked to reduced kidney function, cardiovascular complications, and increased mortality. Limitations of current therapy demonstrate that a new treatment approach such as VS-501 to delay the time to dialysis and also reduce the mortality rate of CKD offers a significant opportunity for improved outcomes with substantial societal benefit.
NIH ExPorter
NIH ExPorter