SUSTAINED RELEASE CYCLOSPORINE FOR TREATMENT OF UVEITIS

这项研究的长期目标是减少或消除葡萄膜炎引起的失明。在这项SBIR的第一阶段，我们开发了为期3年的眼内环孢素装置。我们准备了高剂量和低剂量的装置，验证了灭菌程序，并开始了体内释放率测试。临床前疗效和毒性数据使国家眼科研究所和杜克大学能够启动一项I/II期临床安全性研究。在这项工作圆满完成后，将进行第二阶段/第三阶段的功效研究。因此，这项第二阶段SBIR提案的具体目标是：1.完成在第一阶段开始的药代动力学工作；2.使试验性制造工艺用于商业化；以及3.设计第三阶段临床试验，包括临床中心的选择和检查。控制输送系统(CDS)在药品审批流程的各个方面都有经验。我们的第一个产品VitrasertTM被授权给Chron Vision。出售该设备的特许权使用费使我们能够承诺内部资金，以保证完成这项工作的第三阶段。我们目前正在与一家主要的眼科公司就该产品的许可证进行谈判，以保证在成功完成试验后植入物的商业化。拟议的商业应用在美国约有10万人因葡萄膜炎而单眼或双眼失明。该产品将处于孤儿药物状态，并有一条“快车道”监管途径，这将帮助我们确保其商业可行性。

The broad long term goal of this research is to reduce or eliminate blindness due to uveitis. In phase I of this SBIR we developed 3 year intraocular cyclosporine devices. We prepared high and low dose devices, validated sterilization procedures, and began release rate testing in vivo. Preclinical efficacy and toxicity data has enabled a Phase I/II clinical safety study to be initiated at the National Eye Institute and Duke University. Phase II/III efficacy studies will follow the successful completion of this work. The specific aims of this Phase II SBIR proposal therefore are to: 1. complete the pharmacokinetic work begun in phase 1; 2. adapt the experimental manufacturing process for commercialization; and 3. design the Phase III clinical trials, including selection and inspection of clinical centers. Control Delivery Systems (CDS) has experience in all aspects of the drug approval process. Our first product the VitrasertTM was licensed to Chiron Vision. Royalties from the sale of this device allow us to commit internal funds to guarantee completion of Phase 3 of this work. We are currently negotiating the license for this product with a major ophthalmic company in order to guarantee the commercialization of the implant on the successful completion of the trials. PROPOSED COMMERCIAL APPLICATION Approximately 100,000 people in the USA are blind in one or both eyes because of uveitis. This product will have orphan drug status and a "fast track" regulatory pathway that will help us to ensure its commercial viability.