Archemix Corp and Nuvelo Inc announced that an Investigational New Drug (IND) application was submitted to the US FDA to begin a phase 1 clinical trial with thrombin inhibitor, ARC183, for potential use in coronary artery bypass graft (CABG) surgery, said a company release.
ARC183 is an anti-thrombin aptamer that is being developed as an anticoagulant/anti-thrombotic. The phase 1 clinical trial with ARC183 for use in CABG surgery is expected to begin in the second half of 2004.
"The data we plan to generate from this trial should educate us on the safety and tolerability of ARC183," stated Dr Claude Benedict, head of development at Archemix. "Furthermore, this study will also validate the anticoagulant activity of this novel compound," he said.
"ARC183 has the potential to provide a rapid onset and offset of action not seen with current intravenous anticoagulants," stated Dr Steven R. Deitcher, vice president medical affairs for Nuvelo. He added, "The ability to provide anticoagulation on demand may benefit both medical and surgical patients alike."
"This is an important milestone for our collaboration and demonstrates our mutual commitment to the rapid development of this compound as a replacement for heparin-protamine in CABG surgeries," commented David Fontana, head of programme management and regulatory affairs and ARC183 program leader for Archemix.
According to the American Heart Association, currently more than 500,000 CABG procedures are performed annually in the US, and more than 700,000 are performed worldwide. Heparin is the anticoagulant currently used in the majority of CABG surgeries; however it has significant limitations such as bleeding and heparin-induced thrombocytopenia (HIT). It is also difficult to dose accurately and requires dose monitoring. In addition, heparin requires protamine to reverse its anticoagulant effects.
Experiments in animal models suggest that the potent anticoagulant, ARC183, has many desirable properties for CABG surgeries including rapid onset and predictable anticoagulant effects, reduced bleeding complications, no risk of HIT and most importantly, a very short half-life, negating the need for an antidote. In addition, as an aptamer, ARC183 has all the advantages normally attributed to aptamers, such as high specificity and affinity for its targets, chemical synthesis allowing for scaleable production and stable shelf life.
Aptamers are single-stranded nucleic acids that form well-defined three-dimensional shapes, allowing them to bind target molecules in a manner conceptually similar to antibodies.
ARC183 is the first product candidate in Archemix's aptamer portfolio. In January 2004, a worldwide collaboration agreement was formed with Nuvelo for the development and commercialization of ARC183. Under the terms of the agreement, Archemix will initially lead development and be responsible for all clinical development activities. Nuvelo will have the option to lead commercialization efforts in which both companies may participate. As part of the transaction, Archemix and Nuvelo will equally share all costs associated with the development and marketing of ARC183 and will have 50/50 ownership of the compound.