Prevention of Delayed Cerebral Vasospasm Associated with Subarachnoid Hemorrhage

描述（由申请人提供）：Hope Pharmaceuticals （Hope）是一家小型企业，分销有限系列的专有药品。2007年，霍普从美国国立卫生研究院（NIH）获得了两项正在申请的专利的全球独家授权，这些专利是最近发现的亚硝酸钠的临床应用，包括在神经病学领域。由于该公司目前销售亚硝酸钠注射液，因此拥有现有临床前信息以及有关产品化学和制造的商业秘密的直接优势。霍普的目标是利用这些专业知识，以便尽快获得监管部门对新疗法的批准。美国国立卫生研究院的研究人员在几项研究中使用了Hope的产品，发现亚硝酸钠的施用可以精确地在血流受损的区域实现局部血管扩张。目前市场上还没有靶向血管扩张剂。目前所有的血管扩张剂都是全身性的，必须仔细监测以防止危及生命的低血压。亚硝酸钠可能特别有利于涉及局灶性血流阻塞的疾病，这些疾病与高死亡率相关，并且没有现有治疗方法，例如与蛛网膜下腔出血相关的脑血管痉挛。蛛网膜下腔出血（SAH）约占所有新发中风的5%。在美国，每年约有33,000人受到影响，根据严重程度，其死亡率在30%至70%之间。它还与幸存者的显著发病率相关，近50%的幸存者经历认知和/或功能障碍。脑血管痉挛是SAH的常见并发症。对于那些有症状性血管痉挛的人来说，结果是可怕的。其中多达三分之一的患者死亡，另外三分之一的患者留下了永久性和严重的残疾。美国食品和药物管理局（FDA）认识到与这种情况相关的严重未满足的医疗需求，授予Hope公司开发的亚硝酸钠注射液“快速通道”地位和“孤儿产品”称号，用于治疗与SAH相关的脑血管痉挛。霍普和国家神经疾病和中风研究所（NINDS）签署了一项合作研究与开发协议，以进行临床开发。根据研究新药（IND） #77,633，双方于2007年7月启动了一项1期临床研究，以调查健康志愿者48小时静脉输注亚硝酸盐的安全性和药代动力学。截至2007年12月1日，该研究的临床部分将完成另外5名患者的入组和给药。利用从1期研究中获得的见解，Hope和NINDS正在计划2期临床试验，以进一步评估亚硝酸钠注射液预防迟发性脑血管痉挛和改善蛛网膜下腔出血后神经预后的安全性和有效性。这项拨款申请旨在支持这些二期临床试验。公共卫生相关性：迟发性脑血管痉挛（DCV）是一种与蛛网膜下腔出血（SAH）相关的严重并发症。超过一半的SAH存活患者发生DCV，并经常导致严重残疾或死亡。Hope制药公司的目标是进行临床研究，以确认亚硝酸钠作为一种新的、安全、廉价、设计合理的治疗方法的安全性和有效性，以预防这种疾病，从而减少患蛛网膜下腔出血的患者的可怕发病率和死亡率。

DESCRIPTION (provided by applicant): Hope Pharmaceuticals (Hope) is a Small Business that distributes a limited line of proprietary pharmaceuticals. In 2007, Hope licensed from the National Institutes of Health (NIH) exclusive, worldwide rights to two pending patent applications for recently discovered clinical uses for Sodium Nitrite, including in the area of neurology. Since it currently markets Sodium Nitrite Injection, Hope has the immediate advantage of existing pre-clinical information along with trade secrets about the product chemistry and manufacture. Hope's goal is to leverage this expertise in order to obtain regulatory approval for new treatments as quickly as possible. Using Hope's product in several of its studies, researchers at the NIH discovered that the administration of Sodium Nitrite can achieve localized vasodilation precisely in areas where blood flow has been compromised. No targeted vasodilator exists on the market at present. All current vasodilators act systemically and must be monitored carefully to prevent life-threatening hypotension. Sodium Nitrite may be especially beneficial for conditions that involve focal obstructions of blood flow, that are associated with high mortality, and that have no existing treatments such as cerebral vasospasm associated with subarachnoid hemorrhage. Subarachnoid hemorrhage (SAH) accounts for approximately 5% of all new strokes. In the United States, it affects approximately 33,000 people each year and is associated with high rates of mortality ranging between 30 and 70% depending on severity. It is also associated with significant morbidity in survivors with nearly 50% of survivors experiencing cognitive and/or functional impairments. Cerebral vasospasm is a common complication following SAH. The outcome for those with symptomatic vasospasm is horrific. As many as one-third of these patients die and another third are left with permanent and severe disabilities. Acknowledging the serious unmet medical needs associated with this condition, the Food and Drug Administration (FDA) granted "Fast Track" status and "Orphan Product" designation to Hope's development of Sodium Nitrite Injection for the treatment of cerebral vasospasm associated with SAH. Hope and the National Institute of Neurological Diseases and Stroke (NINDS) executed a Collaborative Research and Development Agreement to conduct clinical development. Under Investigational New Drug (IND) #77,633, the parties initiated a Phase 1 clinical study in July 2007 to investigate the safety and pharmacokinetics of a 48-hour intravenous nitrite infusion in healthy volunteers. As of December 1, 2007, the clinical component of this study will be completed with the enrollment and dosing of five additional patients. Using the insights gained from the Phase 1 study, Hope and NINDS are planning Phase 2 clinical trials as further evaluation of the safety and efficacy of Sodium Nitrite Injection for the prevention of delayed cerebral vasospasm and the improvement of neurological outcomes after subarachnoid hemorrhage. This grant application is intended to support these Phase 2 clinical trials. PUBLIC HEALTH RELEVANCE: Delayed cerebral vasospasm (DCV) is a serious complication associated with subarachnoid hemorrhage (SAH). DCV occurs in over half of the patients that survive SAH and frequently causes significant disability or death. Hope Pharmaceuticals' objective is to conduct clinical studies to confirm the safety and efficacy of Sodium Nitrite as a new, safe, inexpensive, and rationally designed therapy to prevent this condition and thereby reduce the horrific morbidity and mortality sustained by patients who suffer a subarachnoid hemorrhage.