Anti-factor IXa/X bispecific antibody (ACE910): hemostatic potency against ongoing bleeds in a hemophilia A model and the possibility of routine supplementation.

摘要: SummaryBackground We previously reported that a humanized anti-factor IXa/X bispecific antibody, hBS23, mimics the function of FVIII even in presence inhibitors, and has preventive hemostatic activity against bleeding an animal model acquired hemophilia A. After further molecular engineering we recently identified improved ACE910, for clinical investigation. Objectives To elucidate in vivo potency ACE910 by examining its effect ongoing bleeds, to determine pharmacokinetic parameters discussion prophylactic use. Methods A non-human primate hemophilia A was established injecting anti-primate neutralizing antibody. When bleeds emerged following artificial bleed-inducing procedure, either or recombinant porcine (rpoFVIII) intravenously administered. rpoFVIII additionally administered twice daily on 2 days. Bleeding symptoms were monitored 3 days. A study multiple-dosing simulations also performed. Results A single bolus 1 3 mg kg−1 showed comparable 10 U kg−1 (twice daily) bleeds. The determined included long half-life (3 weeks) high subcutaneous bioavailability (nearly 100%). simulation results based indicated above level could be maintained with once-weekly administration suggesting possibility more effective prophylaxis. Conclusions ACE910 may offer alternative on-demand treatment option patients hemophilia A, as well user-friendly aggressive routine supplementation.