Hemostatic properties of the FVIIa analog NN1731

Recombinant activated coagulation factor VII (rFVIIa) has proven to be a useful prohemostatic agent in patients with hemophilia and antibody inhibitors. It has also been used off-label in other settings. A major mechanism of its hemostatic efficacy is its ability to activate factor X on the surface of activated platelets in a tissue factor (TF)-independent manner. Novel analogs of FVIIa have been designed to have greater platelet-surface activity in the hope that these will be more active and reliable hemostatic agents. The analog NN1731 (vatreptacog alfa) was designed to have greater activity in the absence of TF, with the same substrate specificity as FVIIa. Surprisingly, it also binds to a greater number of sites on activated platelets by an, as yet, unknown mechanism. This molecule exhibits greater potency than FVIIa in biochemical assays, in vitro and animal models, and in early phase clinical trials.