The bispecific factor VIII–mimetic antibody ACE910 has a longer half-life than current hemophilia A treatments, potentially offering a more convenient once-weekly, subcutaneous injection, based on a study published in Blood.
In a phase I study, ACE910 was well tolerated at doses up to 1 mg/kg, with an average half life of 28 to 34 days. Based on tests in FVIII-depleted plasma, ACE910 shortened activated partial thromboplastin time (APTT) and increased peak height of thrombin generation, and exhibited a long-lasting response throughout the 24-week study period. ACE910 at 1 mg/kg resulted in APTT similar to that seen in normal plasma, although the peak height of thrombin generation did not reach normal levels.
The findings suggest “that ACE910 has the potential to reduce bleeding frequency in patients with severe hemophilia A to that of patients with mild hemophilia A, even at less frequent dosing, compared with existing FVIII and bypassing drugs. Furthermore, ACE910 may change the treatment paradigm from the current approach of maintaining trough levels of FVIII:C greater than 1% to a new approach of maintaining a constant hemostatic activity corresponding to a mild hemophilia A level,” wrote Dr. Naoki Uchida of Showa University Clinical Research Institute for Clinical Pharmacology and Therapeutics, Tokyo, and colleagues (Blood. 2016 Apr 7. doi: 10.1182/blood-2015-06-650226 ).
Adverse events were comparable with those of placebo; 13 of 48 subjects who received ACE910 reported 15 adverse events, compared with 6 adverse events reported by 4 of 16 subjects who received placebo. Except for moderate nasopharyngitis reported in one subject, all adverse events were mild, were not dose dependent, and were similar for Japanese and white subjects. Clinical and laboratory findings showed normal coagulability with ACE910 administered at any dose.
An anti-drug antibody response was observed in 2 of 48 patients (1 Japanese, 1 white) both at 0.1 mg/kg ACE910. The anti-drug antibody responses were not IgE mediated, and no allergic symptoms were observed.