ARC-1779, a PEGylated aptamer antagonist of von Willebrand factor for potential use as an anticoagulant or antithrombotic agent.

Archemix Corp's ARC-1779 is an optimized, second-generation, PEGylated aptamer that exerts a novel antithrombotic action through targeting the A1 domain of activated von Willebrand factor (vWF) and inhibiting the binding of platelet receptor glycoprotein Ib, thus reducing platelet adhesion, aggregation and thrombus growth in arterial beds. By inhibiting vWF-dependent arterial thrombogenesis, ARC-1779 has potential therapeutic benefit in acute coronary syndromes and von Willebrand's disease, as well as in vWF-related platelet disorders such as thrombotic thrombocytopenic purpura (TTP) and other thrombotic microangiopathies. As an aptamer, the actions of ARC-1779, unlike other antiplatelet agents, can be readily reversed by binding to a complementary sequence of oligonucleotides; this ability offers potential therapeutic benefit in surgery. In phase I and II clinical trials, ARC-1779 has exhibited favorable pharmacokinetic, pharmacodynamic and safety properties in healthy individuals and patients with TTP. At the time of publication, phase II trials in patients with TTP and thrombosis were ongoing or recruiting patients. Further phase II and III trials are necessary and highly anticipated to establish the therapeutic potential of ARC-1779 as an antithrombotic agent.