Arterial thrombosis — roxifiban acetate
Thrombus formation is a continuous process within the cardiovascular circulation, as it is a part of the body's normal repair system. However, when this becomes excessive, it can be dangerous and result in myocardial infarction. Clots within the venous system are treated with agents such as heparin and warfarin, but these drugs are of much more limited use for treating arterial thrombus formation.
The thrombus formation process is initiated by platelet aggregation. Various antiplatelet drugs that are of some help are on the market, including ticlodipine and aspirin. They are effective against some but by no means all of the platelet activators that act within the body. As the drugs' activity is limited, serious thromboembolic complications are still common in treated patients, and more effective drugs are still needed.
One such drug that is in development at Bristol-Myers Squibb is roxifiban acetate, previously known as DMP 754.1 Roxifiban is a pro-drug of XV459, a potent antiplatelet agent that has a high affinity and specificity for platelet active glycoprotein (GP) IIb/IIIa receptors. The ester pro-drug is hydrolysed to the active free acid form on oral administration, which has a comparable high affinity for both resting and activated platelets, and a relatively slow rate of dissociation from resting platelets.2 Phase I trials showed it to be fairly well tolerated, and give a sustained systemic drug exposure over the whole period of administration.3
Roxifiban is now in Phase III trials, being administered in combination with aspirin, as a treatment for moderate to severe peripheral arterial disease. If it succeeds, then it has the potential to be a significant improvement on currently available treatments for arterial clots.