New drug VS-501 for treating hyperphosphatemia in chronic kidney disease

治疗慢性肾病高磷血症的新药VS-501

基本信息

批准号：
8389307
负责人：
Jinshyun Ruth Wu-Wong
金额：
$ 21.74万
依托单位：
VIDASYM, INC.
依托单位国家：
美国
项目类别：
财政年份：
2012
资助国家：
美国
起止时间：
2012-09-01 至 2014-04-30
项目状态：
已结题

来源：
https://reporter.nih.gov/project-details/8389307
关键词：
Adverse effects Albumins Aluminum Americas Annual Reports Appearance Binding Budgets Calcium Carbonates Cardiovascular Diseases Cardiovascular Physiology Cardiovascular system Chronic Kidney Failure Clinical Clinical Pathology Clinical Trials Creatinine Deterioration Development Dialysis patients Dialysis procedure Disease Disease Progression Dose Exhibits Fibrosis Foundations Gastrointestinal tract structure General Population Goals Health Healthcare Healthcare Systems Heart Human Hypercalcemia Individual Information Systems Kidney Kidney Diseases Knowledge Lead Link Marketing Medical Medicare Metabolism Minerals Modality Modeling Normal Range Oral Organ Outcome Patients Penetration Pharmaceutical Preparations Phase Plants Polymers Process Proteins Rattus Renal Osteodystrophy Renal function Resuscitation Risk Safety Sales Sampling Serum Small Business Innovation Research Grant Staging Survival Rate Testing Therapeutic Time Toxicology Treatment Cost Treatment Efficacy Urine Weight Western Blotting base cardiovascular disorder risk commercial application experience food consumption gastrointestinal head-to-head comparison improved inflammatory marker inorganic phosphate mortality novel patient population phase 1 study phase 2 study pill protective effect safety study scale up sevelamer technological innovation urinary

项目摘要

DESCRIPTION (provided by applicant): 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.

描述（由申请人提供）：美国有 2600 万人患有慢性肾病 (CKD)。尽管 CKD 患者可以采用多种治疗方法，但五年生存率约为 33%。 CKD 中血清磷酸盐水平控制不当可导致各种具有临床意义的病理，例如肾功能进一步恶化、心血管并发症、肾性骨营养不良和死亡率增加。目前市场上的口服磷酸盐结合剂存在严重缺点：（1）磷酸盐结合效果不佳且效率低下，（2）药丸负担高（每天服用大量药丸），味道不佳，因此依从性低，（3）价格昂贵，尤其是钙剂-不含磷酸盐结合剂，以及（4）副作用和安全问题，例如高钙血症、铝中毒、对其他药物的负面影响、胃肠道（GI）副作用和器官积聚。 Vidasym 采用独特的方法来发现 VS-501，这是一种从植物中提取的天然聚合物，经过化学处理，可以高效吸收胃肠道中的磷酸盐和其他矿物质，而不会产生全身毒理学效应。为了确认 VS-501 卓越的安全性和有效性，重要的一步是在临床验证的 5/6 肾切除术（NX）中对 VS-501 和司维拉姆（目前市场上首选的磷酸盐结合剂）进行头对头比较。）尿毒症大鼠模型。因此，本一期研究的具体目的是：（1）比较VS-501和碳酸司维拉姆对5/6 NX尿毒症大鼠的治疗效果。验收标准：VS-501将比碳酸司维拉姆表现出更好的疗效和更少的副作用； (2) 阐明 CKD 中磷酸盐控制对肾脏和心血管的益处。验收标准：VS-501将比司维拉姆表现出更好的心脏和肾脏保护作用。实现这些目标将证实 VS-501 作为治疗 CKD 高磷血症的临床候选药物的优越性，并证明磷酸盐控制对改善 CKD 疾病进展和心血管并发症的功效，这将导致 II 期 IND 启动研究（安全性和毒理学）VS-501。 II期研究的完成将使VS-501进入人体临床试验。 Vidasym 计划将 VS-501 开发为治疗 CKD 的可报销处方新药。一旦开发出来，这种药物不仅会降低 CKD 的死亡率，还会减少透析的需要。目前磷酸盐结合剂的全球年销售额达到 1 亿美元以上，主要用于透析患者。仅司维拉姆一项的全球年销售额就达 7.5 亿美元。从销售数量来看，美国 >90% 的透析患者接受磷酸盐结合剂治疗，但只有 <1% 的 3/4 期 CKD 患者接受治疗。假设 VS-501 在 3/4/5 期 CKD 患者群体（约 20 名 MM 患者）中的渗透率为 3%，年治疗费用为 2,000 美元（司维拉姆的年治疗费用为约 3000 美元），则预计美国年销售额将为12亿美元。公共健康相关性：Vidasym 的 I 期 SBIR 研究将调查使用 Vidasym 的新型磷酸盐结合剂 Vida-501 治疗高磷酸盐血症并改善慢性肾脏病 (CKD) 患者的肾脏和心血管功能的可行性。全球有超过 3.5 亿人患有 CKD，预计到 2025 年这一数字将增加到超过 5.5 亿。尽管有多种治疗 CKD 的方法和药物，但 CKD 患者的死亡率仍然很高（~33%），并且透析 CKD 的数量患者不断增加。医学界迫切需要开发一种有效且新颖的复苏方法来治疗 CKD。 CKD 中的高磷血症与肾功能下降、心血管并发症和死亡率增加有关。当前治疗的局限性表明，诸如 VS-501 之类的新治疗方法可以延迟透析时间并降低 CKD 死亡率，为改善结果提供了重要机会，并具有巨大的社会效益。