BAY 94-9027 prophylaxis is efficacious and well tolerated for up to >5 years with extended dosing intervals: PROTECT VIII extension interim results

Abstract

Introduction: BAY 94-9027 is an extended‒half-life, site-specifically PEGylated, B-domain‒deleted recombinant factor VIII (FVIII). The PROTECT VIII main study demonstrated efficacy of bleed control using extended-interval prophylaxis with BAY 94-9027 for 36 weeks. Aim: To report long-term efficacy and safety of prophylaxis with BAY 94-9027 in a descriptive analysis of the ongoing PROTECT VIII extension with a total treatment time of up to >5 years. Methods: Previously treated males aged 12-65 years with severe haemophilia A who completed the PROTECT VIII main study were eligible for the open-label extension. Patients received on-demand treatment or prophylaxis (30‒40 IU/kg twice weekly, 45‒60 IU/kg every 5 days, or 60 IU/kg every 7 days) and could switch regimens as needed. Results: Patients (N = 121; on demand, n = 14; prophylaxis, n = 107) accumulated a median (range) of 3.9 years (297‒1965 days) and 223 (23‒563) total exposure days by 31 January 2018. During the extension, median (quartile [Q]1; Q3) annualized bleeding rates (ABRs) for total bleeds were 1.6 (0.3; 4.6) for patients receiving prophylaxis and 34.1 (20.3; 36.6) for patients receiving on-demand treatment. ABRs for twice-weekly (n = 23), every-5-days (n = 33), every-7-days (n = 23) and variable frequency (n = 28) treatments were 1.7, 1.2, 0.7 and 3.1, respectively. Of prophylaxis patients, 20.6% were bleed-free throughout the extension (median time, 3.2 years), and 44.5% were bleed-free during the last 6 months. No patients developed FVIII inhibitors. Conclusions: BAY 94-9027 prophylaxis was efficacious and well tolerated with dosing intervals up to every 7 days for a median (range) of 3.9 years (0.8-5.4 years).