Sutra TMVR delivery system development and V&V testing

项目摘要 二尖瓣返流（MR）是美国最常见的心脏瓣膜病。 4.1在美国，有100万中重度二尖瓣返流患者需要治疗。但只有 美国每年约有50，000名患者因MR而接受手术， 手术的复杂性和病人的安全在心脏瓣膜中有很大的热情 行业和临床医生开发经导管二尖瓣修复术（TMVRep）和置换术 （TMVR），为MR患者提供微创治疗选择。经过十多年的 在开发过程中，只有一种器械，即MitraClip，已获得FDA批准，并已上市销售。 available.虽然MitraClip安全且具有已证实的临床受益，但无法有效消除二尖瓣返流 在所有患者中，即使是轻度MR也与发病率和死亡率增加相关。TMVRep 而正在开发的TMVR设备仅对精心挑选的患者安全有效。 在该提案中，Dura Biotech建议开发新型Sutra半瓣膜TMVR 该系统结合了外科二尖瓣置换术、TMVR和TMVRep的最佳方面 为MR提出一种优雅有效的解决方案。植入Sutra半瓣膜 TMVR系统用新型三叶人工瓣膜替代自体二尖瓣后叶 其在设计和功能上模仿天然二尖瓣后叶，以提供可预测和 一致的二尖瓣返流减少。由于Sutra半瓣膜TMVR系统仅覆盖后部 二尖瓣的一部分，它消除了左心室流出道梗阻常见的其他 更换器械，并实现更小的器械外形，以实现安全的经中隔入路， 交付. Sutra半瓣膜TMVR系统的可行性已通过以下方式得到证明： 严格的实验室和临床前动物试验。 该CRP项目的目标是完成后期开发， 新型Sutra半瓣膜TMVR系统的商业化。为实现这一目标， 在本项目中，Sutra输送系统将通过GLP体内动物研究进行优化。在 目标2，将对最终的Sutra系统设计进行验证和确认测试， 数据将用于向FDA提交早期可行性研究（EFS）申请。 成功完成这一CRP项目将有助于杜拉跨越“死亡之谷”之间的 开发和商业化，以帮助将Sutra半瓣膜TMVR系统推向市场 并为数百万患有MR的患者提供几乎没有治疗选择的服务。

PROJECT SUMMARY Mitral regurgitation (MR) is the most prevalent valvular heart disease in the U.S. There are 4.1 million patients in the US with moderate to severe MR requiring treatment. However, only approximately 50,000 patients in the U.S. undergo surgery for MR each year due to concerns about procedural complexity and patient safety. There is great enthusiasm among the heart valve industry and clinicians to develop transcatheter mitral valve repair (TMVRep) and replacement (TMVR), offering less invasive treatment options for MR patients. After more than a decade of development, only one device, the MitraClip, has been approved by the FDA and is commercially available. While safe with proven clinical benefits, the MitraClip is not effective in eliminating MR in all patients, and even mild MR is associated with increased morbidity and mortality. TMVRep and TMVR devices in development are only safe and effective for carefully selected patients. In this proposal, Dura Biotech proposes to develop the novel Sutra Hemi-valve TMVR system which combines the best aspects of surgical MV replacement, TMVR, and TMVRep approaches to pose an elegant and effective solution for MR. The implanted Sutra Hemi-valve TMVR system replaces the native posterior mitral leaflet with a novel tri-leaflet prosthetic valve that mimics the native posterior mitral leaflet in design and function, to provide predictable and consistent MR reduction. Because the Sutra Hemi-valve TMVR system only covers the posterior portion of the MV, it eliminates left ventricular outflow tract obstruction seen commonly with other replacement devices, and enables a smaller device profile for safe, trans-septal access and delivery. The feasibility of the Sutra Hemi-valve TMVR system has been demonstrated through rigorous bench and preclinical animal testing. The goal of this CRP project is to finalize the late stage development and commercialization of the novel Sutra Hemi-valve TMVR system. To achieve this goal, in aim 1 of this project, the Sutra delivery system will be optimized through GLP in vivo animal studies. In aim 2, verification-and-validation tests will be performed on the final Sutra system design, and the data will be complied for submission of an Early Feasibility Study (EFS) application to the FDA. Successful completion of this CRP project will help Dura cross the “valley of death” between development and commercialization to help bring the Sutra Hemi-valve TMVR system to market and serve millions of patients suffering from MR with little-to-no treatment options.