Development of long-acting recombinant FVIII and FIX Fc fusion proteins for the management of hemophilia.
BACKGROUND
Prophylactic treatment with replacement clotting factor is the recommended regimen for patients with severe hemophilia to prevent bleeding episodes. However, currently available replacement clotting factors are limited by their relatively short half-lives and require intravenous injections up to three times weekly to maintain protective levels, which can impact compliance and, thus, patient outcomes.


METHODS
The potential advantages of long-acting coagulation factors, including reduced injection frequency, increased treatment adherence, and improved clinical outcomes, are discussed. Fragment crystallizable (Fc) fusion technology is introduced and the development of long-acting recombinant factor VIII Fc (rFVIIIFc) and recombinant factor IX Fc (rFIXFc) fusion proteins for the treatment of hemophilia A and B, respectively, are described. Preclinical and clinical studies of rFVIIIFc and rFIXFc showing improved pharmacokinetics over currently available products are reviewed.


CONCLUSIONS
Long-acting coagulation factors, including rFVIIIFc and rFIXFc, have the potential to change current paradigms of care for hemophilia A and B, respectively. Less frequent infusions may provide prolonged protection from bleeding and bleed resolution with fewer injections. In addition, long-acting coagulation factors provide an opportunity for improved individualized treatment for hemophilia.
Indiana Hemophilia & Thrombosis Center, 8204 Harcourt Road, Suite 500, IN 46260, USA. ashapiro@ihtc.org
Amy
A
Shapiro
D000818:Animals; D002986:Clinical Trials as Topic; D004353:Drug Evaluation, Preclinical; D005164:Factor IX / Q000737:chemistry*; D005169:Factor VIII / Q000737:chemistry*; D006467:Hemophilia A / Q000188:drug therapy*; D006801:Humans; D011993:Recombinant Fusion Proteins / Q000009:adverse effects / Q000493:pharmacokinetics / Q000627:therapeutic use*
D011993:Recombinant Fusion Proteins; D005169:Factor VIII; D005164:Factor IX