Prevention of Delayed Cerebral Vasospasm Associated with Subarachnoid Hemorrhage

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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.