Viprinex™ (ancrod) has been studied in nearly 2400 patients worldwide in clinical studies for ischemic stroke. Based on the results of the ongoing clinical studies, Viprinex may have the potential to double the treatment window following the onset of stroke. Currently, the only approved therapy for stroke that has been shown to reduce stroke related disability must be administered within three hours of stroke onset, limiting the number of patients who may be treated.
A stroke occurs when a blood clot is obstructs blood flow to part of the brain, depriving brain tissue of oxygen and nutrients. Obstructed blood flow leads to loss of brain cell function causing loss of vital functions such as speech and mobility. If the obstruction to blood flow persists it will lead to brain cell death and permanent disability. The primary goal for the treatment of acute ischemic stroke is to restore blood flow to the affected area of the brain.
Ancrod, an enzyme derived from the venom of the Malayan pit viper, is a novel Fibrinogen Reducing Agent (FRA) that reduces blood levels of fibrinogen, the primary protein involved in blood clotting. In this way, it acts as an anticoagulant. In addition, reducing fibrinogen in the blood it also reduces blood viscosity, which may improve blood flow to the affected areas of the brain. Furthermore, as the fibrinogen is broken down, natural mechanisms are activated to dissolve preformed blood clots. Since Viprinex acts in the blood for several hours, its effect on blood flow should be sustained longer than with existing therapy.
A randomized, double-blind, placebo-controlled U.S. Phase 3 clinical study of 500 stroke patients was completed in 1998 evaluating the safety and efficacy of ancrod given within three hours of stroke of acute ischemic stroke. In that study, ancrod was shown to be effective in reducing stroke related disability. A separate randomized, double-blind, placebo-controlled Phase 3 study was completed in Europe in 2000, enrolling patients within six hours of onset of acute ischemic stroke. The trial was stopped after a planned interim analysis indicated lack of efficacy. In the final analysis, the incidence of intracranial hemorrhage and mortality was greater in the ancrod treated group. The higher dosing levels in the European trial and the use of protocol criteria that permitted entry of patients at higher risk of hemorrhage are thought to have contributed to the these findings.
A retrospective analysis of the relative strength of the positive U.S. findings versus the neutral European findings has suggested the need for a revised ancrod dosing strategy. This new dosing strategy is being used in the current Phase 3 program.
MEAN PLASMA FIBRINOGEN CONCENTRATIONS
1. Brief infusion can produce desired fibrinogen pattern extending for several days.
2. Time course of fibrinogen as seen here similar to that reported after IV infusion of 1-2 IU/kg over 4-6 hours in normal subjects patients.
3. Other studies showed dose-related decreases with different infusion regimens over 3hrs, 6hrs and 24hrs.
ABOUT STROKE
According to the American Stroke Association, every 45 seconds someone in the U.S. suffers a stroke and every three minutes someone dies of one. It is the nation’s third leading cause of death after diseases of the heart and all forms of cancer and is the leading cause of serious, long-term disability.
LA stroke occurs when a blood vessel that carries oxygen and nutrients to the brain is either blocked by a clot (ischemic) or ruptures (hemorrhagic). Brain tissue that is deprived of oxygen and nutrients begins to die, causing loss of motor function, alteration of or loss of speech and/or vision. It is estimated that less than ten percent of stroke patients are eligible for current therapy and less than five percent actually receive treatment. The estimated direct and indirect costs of stroke in the U.S. in 2004 were estimated to be $53.6 billion.