Clinical investigation of desmoteplase in acute ischemic stroke: rationale and progress

Monica Millan, Antoni Davalos

The thrombolytic agent desmoteplase produced by recombinant biotechnology has its natural place in the saliva of the vampire Desmodus rotundus. The structure of desmoteplase is similar to tissue plasminogen activator, but it does not contain the lysine-binding Kringle 2 domain. Accordingly, desmoteplase has higher fibrin specificity, absence of neurotoxicity and a better profile in terms of plasma half-life compared with tissue plasminogen activator in experimental stroke models. The Phase II trials DIAS and DEDAS indicated that intravenous desmoteplase administered within 3–9 h after stroke onset at doses up to 125 µg/kg was associated with a low rate of symptomatic intracranial hemorrhage and a high rate of reperfusion that correlated with clinical benefit. The subsequent DIAS-2 study did not show the same benefit, probably owing to the inclusion of a substantial number of patients with mild strokes and small mismatch volumes associated with no vessel occlusion. A post hoc analysis of the DIAS-2 data showed a clinical benefit of desmoteplase in those patients with proximal arterial occlusion on baseline angiography that lead to the planning and development of the ongoing DIAS-3 and DIAS-4 studies, whose results will determine whether desmoteplase could be used as a treatment for acute ischemic stroke