Clinical Utility of Subcutaneous Factor VIII Replacement Therapies in Hemophilia A: A Review of the Evidence

Abstract

Hemophilia therapies have tremendously improved over the last decades with the development of prolonged half-life factor VIII (FVIII) and FIX concentrates, non-factor therapies, such as emicizumab, anti-TFPI antibodies or siRNA antithrombin and gene therapy. All of these new molecules significantly reduced the burden of the disease and improved the quality of life of patients with severe hemophilia. Emicizumab, a non-factor therapy, is currently the only subcutaneous molecule available for prophylactic treatment of severe hemophilia A. Because of the subcutaneous route of delivery and similar efficacy to FVIII replacement therapy, emicizumab has been rapidly adopted by patients and their families. This clinical observation emphasizes the relevance and need for the development of subcutaneous FVIII concentrates. Here, we report evidence-based advantages and interest in the subcutaneous route of administration for the treatment of hemophilia A and review the stages of development of the different subcutaneous FVIII molecules.

Keywords:

• hemophilia A
• factor VIII
• recombinant von Willebrand factor fragment
• prophylaxis
• subcutaneous injection

Disclosure

Y. Dargaud has received grants/research support from Bayer, Baxter, Baxalta, Novo Nordisk, CSL Behring, LFB, Pfizer, LeoPharma, Octapharma and Stago; an educational grant from Takeda and honoraria from Bayer, Baxter, Novo Nordisk, CSL Behring, Sobi and Octapharma. M. Janbain reports consultancy fees, honoraria, and/or speaker bureau from Genentech, Takeda, Bayer, BioMarin, and CSL Behring, outside the submitted work. The authors report no other conflicts of interest in this work.