EP217609 and its specific antidote avidin (Endotis Pharma) were found to be well tolerated in phase I studies. Data from these studies in healthy subjects were presented at the XXIII Congress of the International Society on Thrombosis and Haemostasis (Kyoto, Japan, 23-28 July 2011).
EP217609 and avidin are currently being investigated in a phase IIa proof-of-concept study, called NOVEL 1 to improve the management of anticoagulation during open-heart surgery. Endotis believes that EP217609 and avidin may provide an alternative treatment to the current standard of care, unfractionated heparin and its antidote protamine.
“The phase I data presented at the International Society on Thrombosis and Haemostasis Congress show that EP217609 produces a predictable and stable anticoagulation, which was rapidly and permanently reversed by avidin after 90 minutes, the average time for open-heart surgery,” said Eric Neuhart, head of clinical research and development, Endotis. “This study is one of three phase I clinical studies that Endotis has conducted to date with EP217609 and avidin in more than 80 healthy subjects. The results are very encouraging and allowed the initiation of the NOVEL I phase IIa study.”
In the study presented, a total of 36 healthy subjects were randomised in nine groups between three EP217609 doses (4, 8, 12 mg) and three avidin/EP217609 molar ratios (1:1, 2:1, 3:1). Overall, EP217609 and avidin were well tolerated. A single intravenous bolus of EP217609 resulted in a dose-dependent increase in standard coagulation tests while the two higher doses completely abolished thrombin generation. Avidin, administered as a 30 min IV infusion, triggered a rapid and irreversible neutralisation of the EP217609 anticoagulant activity without rebound effect (at the two higher ratios).
About EP217609 and avidin
EP217609 consists of a fondaparinux analog coupled to a direct thrombin inhibitor and linked to a biotin moiety. Once added, avidin binds extraordinarily tightly to the biotin segment and permanently destabilises the structure of the molecule. The half lives of EP217609 (~20 hours) and avidin (~15 minutes) are well suited for emergency cardiovascular care during cardiac surgery.