Non-Clinical and Clinical Characterization of a Novel Acting Thrombolytic: Alfimeprase

Alfimeprase (ALF) is a recombinant, truncated form of fibrolase, a directly fibrinolytic zinc metalloproteinase that was first isolated from the venom of the Southern copperhead snake (Agkistrodon contortrix contortrix). ALF has direct proteolytic activity against the fibrin(ogen) Aα chain. ALF can be covalently bound and neutralized by serum α 2 -macroglobulin, a prevalent mammalian protease inhibitor. Preclinical pharmacology studies have shown that thrombolysis with ALF is up to 6-times more rapid than with select plasminogen activators. Additional studies suggest that intra-thrombus ALF has the potential to be a fast and effective thrombolytic without generation of a systemic lytic state. Investigations of phases 1 and 2 indicate that ALF is active and generally well tolerated. This paper reviews the biochemical characteristics of ALF and a review of the preliminary clinical experience in subjects with acute peripheral arterial occlusion and in those with central venous access device occlusion.