Long Acting EPO For Treating Chronic Kidney Disease

描述(申请人提供)：贫血是慢性肾脏疾病(CKD)患者的常见症状，90%以上的CKD患者患有终末期肾脏疾病。贫血通常是由于患病的肾脏无法产生促红细胞生成素(EPO)而引起的。贫血会导致疲劳，降低生活质量，并与CKD患者死亡率的增加相关。重组EPO能有效逆转约90%的CKD患者的贫血。2002年，重组促红细胞生成素产品在全球的销售额约为40亿美元，用于治疗继发于慢性肾脏病的贫血，使促红细胞生成素成为产品总销售额最高的肾脏疾病药物。促红细胞生成素的循环半衰期很短，通常每周给患者服用两到三次。BOLDER生物技术创造了一种高效、长效的EPO类似物，与EPO相比，这种类似物在动物红细胞生成模型中的循环半衰期显著延长，疗效优越。基于动物研究，我们预计我们的长效EPO类似物在人类身上每4-8周给药一次将是有效的。这种新型促红细胞生成素类似物的体内特性得到改善，将减少频繁注射的需要，改善患者的生活质量，并可能导致改善治疗效果。我们的长效促红细胞生成素类似物有可能通过减少患者所需的药量、减少与患者到治疗中心就诊相关的成本以及通过减少医护人员与提供治疗相关的时间来显著降低医疗成本。由于其独特的结构，我们的长效EPO类似物的制造成本预计将显著低于其他EPO产品。这项提案的目标是开发这种长效促红细胞生成素类似物，用于治疗与慢性肾脏病相关的贫血。在这项建议的第一阶段，我们将优化制造流程，开发和验证辅助分析方法，以生产用于GLP(良好实验室实践)药理学和毒理学研究的材料。在第一阶段，我们还将为人类第一阶段安全性和第二阶段剂量范围疗效研究设计临床方案。第二阶段的SBIR建议将包括提交研究新药申请，为临床试验生产GMP(良好制造实践)材料，以及第一阶段和第二阶段临床试验的表现。我们长效促红细胞生成素类似物的成功开发将为CKD患者提供一种更持久、更便宜的有效治疗贫血的替代方案

DESCRIPTION (provided by applicant): Anemia is a frequent finding in patients with chronic kidney disease (CKD) and is present in over 90 percent of CKD patients with end-stage renal disease. Anemia typically results from inability of the diseased kidney to produce erythropoietin (EPO), which stimulates production of red blood cells. Anemia leads to fatigue, a decreased quality of life and correlates with increased mortality in CKD patients. Recombinant EPO is effective at reversing anemia in about 90 percent of CKD patients. Recombinant EPO products had worldwide sales of about $4 billion in 2002 for treating anemia secondary to CKD, making EPO the single most expensive renal disease medicine in terms of total product sales. EPO has a short circulating half-life and generally is administered to patients two to three times per week. Bolder BioTechnology has created a highly potent, long-acting EPO analog that has a significantly increased circulating half-life and superior efficacy in animal erythropoiesis models compared to EPO. Based upon animal studies we anticipate that our long acting EPO analog will be effective when administered once every 4-8 weeks in humans. The improved in vivo characteristics of this novel EPO analog will reduce the need for frequent injections, improve patient quality of life and potentially lead to improved therapeutic efficacy. Our long-acting EPO analog has the potential to significantly reduce healthcare costs by reducing the amount of drug required by patients, by reducing costs associated with patient visits to treatment centers and by reducing healthcare worker time associated with providing treatments. Because of its unique structure, manufacturing costs for our long acting EPO analog are anticipated to be significantly less than for other EPO products. The goal of this proposal is to develop this long-acting EPO analog for the treatment of anemia associated with CKD. During Phase I of this proposal, we will optimize the manufacturing process and develop and validate supporting assay methods to produce material for GLP (Good Laboratory Practices) pharmacology and toxicology studies. During Phase I we also will design clinical protocols for Phase I safety and Phase II dose ranging efficacy studies in humans. The Phase II SBIR proposal will include filing of an Investigational New Drug application, production of GMP (Good Manufacturing Practices) material for clinical trials, and performance of the Phase I and Phase II clinical trials. Successful development of our long-acting EPO analog will provide CKD patients with a longer-acting, significantly less expensive alternative for the effective management of anemia