The studies examined the anticoagulant and antiplatelet activities of MC-45308 in both in vitro and in vivo experiments.
The anticoagulant effects of MC-45308 were evaluated with a series of recognized lab tests used to monitor the clotting ability of whole blood. The global anticoagulant assay was used to compare MC-45308 to the clinically approved anticoagulants bivalirudin (The Medicines Company’s Angiomax) and Argatroban (GlaxoSmithKline). In this test, MC-45308 compared favorably to both bivalirudin and Argatroban, by prolonging the activated clotting time further when used at the same concentration.
A second set of experiments involved the rabbit venous stasis model of thrombosis, which is commonly used to screen therapeutic compounds for antithrombotic activities. In this model, MC-45308 was more effective than both bivalirudin and Argatroban when administered intravenously at a dose of 250 micrograms/kg effecting an approximately 80% reduction in clot score.
The comparative bleeding profile of MC-45308, bivalirudin and argatroban were similar in this model, suggesting that MC-45308 may share a similar safety profile.
Medicure also presented data on the antiplatelet effects of MC-45308. When tested against a variety of clinically relevant agonists including ADP, collagen and ristocetin, MC-45308 inhibited aggregation induced by each of these agonists, with the most pronounced effect seen in ADP induced aggregation.
Inhibition of ADP-induced platelet aggregation has proven to be an effective clinical strategy in the management of a number of cardiovascular indications, including acute coronary syndromes, peripheral arterial disease, myocardial infarction and stroke, as evidenced by the success of the antiplatelet drug clopidogrel (Bristol-Myers Squibb’s Plavix).
The preclinical studies demonstrated that MC-45308 has simultaneous anti-platelet and anti-coagulant effects. A drug of this type does not currently exist within the antithrombotic marketplace.
The results also suggest that MC-45308 may be a more effective therapeutic for treatment of thrombotic disorders than existing clinically approved agents.
“Given that MC-45308 performed comparably or better than clinically approved therapeutics in these studies further underscores its potential to be a major drug in the management strategy of cardiovascular diseases such as myocardial infarction, stroke, pulmonary emboli and peripheral arterial disease,” stated Dr Albert Friesen, Medicure’s president and CEO.
Additional experiments to confirm these results and further evaluate MC-45308’s effects are currently underway.