Nuvelo has obtained orphan-drug designation from the Committee for Orphan Medicinal Products of the European Medicines Agency for its lead product candidate, alfimeprase, for the treatment of acute peripheral arterial occlusion (PAO), or "leg attack."
Alfimeprase, an enzyme produced by recombinant DNA technology, possesses a unique mechanism of action. It directly degrades fibrin, producing a rapid dissolution of blood clots. In clinical studies, alfimeprase has been shown to have the ability to degrade large arterial clots within four hours of initiation of dosing, as well as the ability to clear a majority of occluded catheters in 15 minutes or less. In addition, its lytic activity is localized to the site of delivery due to its rapid inhibition by alpha-2 macroglobulin, a naturally occurring protein in the blood, within seconds of its movement away from the clot and into the general circulation. This clearance mechanism helps focus the thrombolytic activity to the site of delivery and, in clinical testing, appears to minimize bleeding side-effects.
PAO is the blocking of arterial blood flow to a lower limb by a blood clot. Affecting more than 100,000 people in the U.S. each year, with similar incidence in Europe, acute PAO is the result of underlying peripheral arterial disease, in which chronic fatty plaque buildup restricts blood flow and is then complicated by the formation of an acute clot. If blood flow is not restored quickly, leg attack can lead to permanent nerve and muscle damage, gangrene, and in the most severe cases, amputation and death.