Long Acting EPO For Treating Chronic Kidney Disease

描述（由申请人提供）：贫血是慢性肾脏病（CKD）患者的常见发现，并且存在于90%以上的终末期肾病CKD患者中。贫血通常是由于患病的肾脏不能产生促红细胞生成素（EPO）而引起的，EPO刺激红细胞的产生。贫血导致疲劳、生活质量下降，并与CKD患者死亡率增加相关。重组EPO可有效逆转约90%的CKD患者的贫血。2002年，重组EPO产品在全球范围内的销售额约为40亿美元，用于治疗继发于CKD的贫血，使EPO成为就产品总销售额而言最昂贵的单一肾病药物。EPO具有短的循环半衰期，通常每周给患者施用两到三次。Bolder生物技术公司已经开发出一种高效、长效的EPO类似物，与EPO相比，该类似物在动物红细胞生成模型中具有显著增加的循环半衰期和上级功效。基于动物研究，我们预期我们的长效EPO类似物在人类中每4-8周施用一次时将是有效的。这种新型EPO类似物的改善的体内特性将减少对频繁注射的需要，改善患者的生活质量，并可能导致改善的治疗效果。我们的长效EPO类似物有可能通过减少患者所需的药物量、减少患者前往治疗中心的相关成本以及减少医护人员提供治疗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着低于其他EPO产品。该提案的目标是开发这种长效EPO类似物，用于治疗与CKD相关的贫血。在本提案的第I阶段，我们将优化生产工艺，并开发和验证支持性测定方法，以生产用于GLP（药物非临床研究质量管理规范）药理学和毒理学研究的材料。在I期研究期间，我们还将设计I期安全性和II期人体剂量范围有效性研究的临床方案。第二阶段SBIR提案将包括提交研究性新药申请，生产用于临床试验的GMP（良好生产规范）材料，以及进行第一阶段和第二阶段临床试验。我们的长效EPO类似物的成功开发将为CKD患者提供一种有效管理贫血的长效、显著便宜的替代方案

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