Alfimeprase
How Alfimeprase Works |
Potential Therapeutic Applications |
Clinical Trials
Commercialization Rights |
Scientific Publications and Presentations
A Recombinant Direct Acting Fibrinolytic
Alfimeprase is a recombinant direct acting fibrinolytic (rDAF), or blood clot dissolver, that has the potential to rapidly and directly degrade fibrin, a protein that provides the scaffolding for blood clots, when delivered through a catheter to the site of a blood clot.
How Alfimeprase Works
When delivered locally at the site of a blood clot, alfimeprase has the potential, through a unique mechanism of action, to directly and rapidly degrade fibrin, a protein that provides the scaffolding for blood clots. In addition, alfimeprase's thrombolytic activity appears to be localized to the site of delivery because it is rapidly inactivated by alpha-2 macroglobulin, a naturally occurring protein in the blood, as it moves away from the site of delivery and into the general blood circulation.
Potential Therapeutic Applications
Alfimeprase is being evaluated as a potential treatment for acute ischemic stroke and catheter occlusion (CO).
Our first target indication is acute ischemic stroke. With approximately 700,000 cases in the United States per year, stroke is the third leading cause of death in the United States and a leading cause of severe, long-term disability. Every 45 seconds someone has a stroke, and every three minutes someone dies of one. A stroke occurs when a blood vessel that carries oxygen and nutrients to the brain either becomes blocked by a blood clot (ischemic stroke) or ruptures (hemorrhagic stroke). This interruption in the blood and oxygen supply, to part of the brain, results in cell death and loss of function. Therapeutic options for patients with stroke are limited due to restrictions on when currently approved drugs can be administered following a stroke and the side effects profiles of these drugs. We believe that a safer, faster acting intra-arterial therapy has the potential to change the treatment paradigm for stroke patients and that a product candidate such as alfimeprase could provide the opportunity to rapidly restore flow and expand the treatment window beyond the current three-hour time frame.
Our second potential indication under evaluation is central venous CO. Patients with cancer and other serious diseases often receive a central venous catheter to deliver vital therapies including chemotherapy, nutritional support, pain management, antibiotics and blood products, and to withdraw blood samples for testing. An estimated five million central venous catheters are placed in patients each year in the United States,1 and approximately 25%, or 1.25 million, become occluded by blood clots.2 Known as CO, this obstruction in a central venous catheter can impair the ability to infuse fluid through or withdraw fluid from the catheter. Because central venous catheters are primarily inserted in patients receiving life-saving medications, it is critical to restore patency (flow) in a timely manner with minimal risk to the patient.
1. Herbst S, McKinnon B. Advances in the treatment of catheter occlusion in the home infusion setting. Infusion 2001: 7.
2. Stephens LC, Haire WD, Kotulak GD. Are clinical signs accurate indicators of the cause of central venous catheter occlusion? J of Parenter Enteral Nutr 1995:19:75-79.
Clinical Trials
We re-initiated the SONOMA-3 (Speedy Opening of Non-functional and Occluded catheters with Mini-dose Alfimeprase) clinical trial in August 2007 to evaluate the efficacy and safety of alfimeprase in patients with occluded central venous catheters in up to 100 patients. In this trial, we are evaluating a single, 10 mg dose of alfimeprase at a concentration of 5 mg/mL. We expect to provide data from this trial in the first half of 2008.
We are enrolling patients in the Phase 2 CARNEROS-1 (Catheter Directed Alfimeprase for Restoration of Neurologic Function and Rapid Opening of Arteries in Stroke) proof-of-concept trial with alfimeprase in acute ischemic stroke. CARNEROS-1 is a multi-center, open-label, dose escalation study beginning with doses of 1 mg, 5 mg and 10 mg, which will enroll approximately 100 patients within 3-9 hours of stroke onset.
Commercialization Rights
We currently have worldwide product rights to alfimeprase.