Half-Life Extended Clotting Factors

Overview

Modified recombinant factor VIII and IX products with extended plasma half-life achieved via Fc fusion, albumin fusion, or PEGylation, reducing infusion frequency below the 2-3x/week required for unmodified factors; factor IX is more amenable due to simpler clearance biology. Factor IX half-life extension was achieved with Fc fusion and albumin fusion products; factor VIII extension was more difficult due to active clearance by activated protein C, but was eventually accomplished with PEGylated versions and an innovative Fc-fusion construct carrying factor VIII on one arm and von Willebrand factor on the other, plus a recombinant polymer. Half-life extended clotting factors reduced infusion frequency below the two-to-three times per week required for standard recombinant factor VIII (half-life 16-18 hours) and factor IX (18-20 hours), though delivery remained intravenous with lyophilized powder reconstitution. (Half-Life Extension Products (05:00-10:00))