title: A bispecific antibody mimicking factor VIII in hemophilia A therapy.
abstract: Serious issues in current hemostatic treatment of hemophilia A are the requirement for frequent intravenous administrations of factor (F) VIII, FVIII inhibitor development, and hemostatic treatment for patients with this inhibitor. For the purpose of overcoming these challenges, the FVIIIa-substituting bispecific antibody against FIXa/FX (ACE910, INN emicizumab) was produced. Emicizumab demonstrated marked hemostatic effects on both ongoing and spontaneous joint bleeding in the acquired hemophilia A primate model. The clinical phase 1 study designed to assess the pharmacokinetics, pharmacodynamics and safety of emicizumab has been initiated. Severe emicizumab-related adverse events were minimal. The t1/2 was approximately 30 days, and bleeding events were significantly decreased by weekly subcutaneous administration in severe hemophilia A patients, independently of the presence of the inhibitor. Currently, the phase 1/2 extension study is ongoing. We anticipate that emicizumab will show the benefits of prophylactic efficacy with subcutaneous administration at a much lower frequency.
authors.affiliation: Department of Pediatrics, Nara Medical University.
authors.forename: Keiji
authors.initials: K
authors.lastname: Nogami
mesh_terms: D000818:Animals; D018033:Antibodies, Bispecific / Q000627:therapeutic use*; D040761:Biomimetic Materials / Q000627:therapeutic use*; D002986:Clinical Trials as Topic; D000529:Complementary Therapies; D015195:Drug Design; D005169:Factor VIII / Q000276:immunology*; D006467:Hemophilia A / Q000188:drug therapy* / Q000276:immunology; D006801:Humans
chemical_list: D018033:Antibodies, Bispecific; D005169:Factor VIII