Drug evaluation: alfimeprase, a plasminogen-independent thrombolytic.

Alfimeprase is an analog of a fibrolase that disrupts formed thrombi through the hydrolysis of fibrin, rather than by activation of plasminogen. Nuvelo Inc, under license from Amgen Inc and together with Bayer AG, is developing this thrombolytic for the potential intravenous treatment of peripheral arterial occlusions and for other cardiovascular indications. Pharmacokinetic studies showed that alfimeprase was rapidly absorbed and achieved therapeutic concentrations at relatively low doses. Preclinical studies showed that adjunctive therapy with antiplatelet agents was necessary to maintain luminal patency. In phase I and II clinical trials alfimeprase effectively thombolysed clots with no drug-related adverse events. However, phase III clinical trials of alfimeprase did not meet their primary endpoints and enrollment in ongoing trials has been suspended pending further analyses and discussion with outside experts and regulatory agencies. In spite of this, the authors conclude that alfimeprase seems to be a lytic agent with much potential. Refinement in its use and dosing needs to be addressed, and further investigation into its pharmacokinetic properties may be worthwhile. Alfimeprase is a drug that is a 'work in progress'.