Pioneering designs for recombinant coagulation factors

Abstract

Coagulation factor replacement therapy has become an established part of the prevention and treatment of bleeding episodes in patients with bleeding disorders, such as hemophilia A, hemophilia B, and von Willebrand disease. Advances in recombinant DNA technology have made it possible to modify recombinant coagulation factor products to enhance their pharmacokinetic properties, biological activity, or other characteristics. CSL Behring has created two novel albumin fusion proteins with the goal of extending the half-life of activated recombinant factor VII (rFVIIa) and recombinant factor IX (rFIX) to allow for less frequent dosing. Preclinical evaluation indicates that the resulting recombinant albumin fusion proteins (rVIIa-FP and rIX-FP) have improved pharmacokinetic properties, including an extended half-life, with preservation of hemostatic efficacy. Clinical evaluation of rIX-FP is now underway in patients with hemophilia B. In addition, we have designed a unique recombinant single-chain factor VIII protein (CSL627) that has improved stability during the manufacturing process and a high affinity for von Willebrand factor, relative to other recombinant factor VIII products. Ongoing studies of rVIIa-FP, rIX-FP, and CSL627 will help further define the potential clinical utility of these novel recombinant proteins in the management of patients with bleeding disorders.