Long Acting EPO For Treating Chronic Kidney Disease

长效 EPO 治疗慢性肾脏病

• 批准号: 6832428
• 负责人: George Norbert Cox
• 金额: $ 25万
• 依托单位: BOLDER BIOTECHNOLOGY, INC.
• 依托单位国家: 美国
• 财政年份: 2004
• 资助国家: 美国
• 起止时间: 2004-09-15 至 2006-08-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/6832428
• 关键词: CHO cells; SDS polyacrylamide gel electrophoresis; anemia; biomedical equipment development; bioreactors; biotechnology; biotherapeutic agent; blood disorder chemotherapy; cell proliferation; chimeric proteins; chronic disease /disorder; cytotoxicity; drug design /synthesis /production; drug screening /evaluation; enzyme linked immunosorbent assay; erythropoietin; high performance liquid chromatography; immunoglobulin G; kidney disorder; laboratory mouse; laboratory rat; nonhuman therapy evaluation; peptide analog; pharmacokinetics; protein purification; recombinant proteins; slow release drug

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

描述（由申请人提供）：贫血是慢性肾脏疾病（CKD）患者的常见发现，并且有超过90％的CKD患有终末期肾脏疾病的患者。贫血通常是由于患病的肾脏无法产生红细胞生成素（EPO）而引起的，从而刺激了红细胞的产生。贫血导致疲劳，生活质量降低，与CKD患者的死亡率增加相关。重组EPO可有效逆转约90％的CKD患者的贫血。重组EPO产品在2002年因治疗继发于CKD的贫血而在全球范围内的销售额约为40亿美元，这使EPO成为产品总销售方面最昂贵的肾脏疾病医学。 EPO的循环半衰期很短，通常每周两到三次。大胆的生物技术创造了一种高度有效的长效EPO类似物，与EPO相比，在动物红细胞生成模型中，循环的半衰期显着增加了，并且具有较高的功效。基于动物研究，我们预计每4-8周在人类中进行一次施用一次，我们的长作用EPO类似物将有效。这种新型EPO类似物的体内特征的改善将减少对频繁注射的需求，提高患者的生活质量，并有可能提高治疗功效。我们的长效EPO模拟有可能通过减少患者所需的药物量来显着降低医疗保健成本，并通过减少与患者访问治疗中心相关的成本，并减少与提供治疗相关的医疗保健工作时间。由于其独特的结构，我们长期表演的EPO模拟的制造成本预计将明显少于其他EPO产品。该提案的目的是开发这种长效的EPO类似物来治疗与CKD相关的贫血。在本提案的第一阶段，我们将优化制造过程，并开发和验证支持分析方法，以生产GLP（良好的实验室实践）药理学和毒理学研究材料。在第一阶段，我们还将设计用于I期安全性和II期剂量范围疗效研究的临床方案。 II期SBIR提案将包括提交研究性新药应用，用于临床试验的GMP（良好的制造实践）材料的生产以及I期和II期临床试验的性能。我们的长效EPO模拟的成功开发将为CKD患者提供更长时间的，较便宜的替代方案，可有效治疗贫血