Objective:
In the PROTECT VIII phase 2/3 trial, the extended–half-life recombinant factor VIII product BAY 94-9027 provided effective bleed protection with twice-weekly, every-5th-day, and every-7th-day prophylaxis for 36 weeks. Herein, we report interim efficacy data from the PROTECT VIII extension study in patients receiving BAY 94-9027 prophylaxis for up to 5.4 years.
Methods:
In the PROTECT VIII trial, previously treated males aged 12 to 65 years with severe hemophilia A received BAY 94-9027 for 36 weeks on demand or for prophylaxis either twice weekly (30–40 IU/kg), every 5 days (45–60 IU/kg), or every 7 days (60 IU/kg). Patients could continue in the extension study using the same or a different regimen. Bleeds were recorded in electronic patient diaries, and annualized bleeding rates (ABRs) were calculated.
Summary:
Of 134 patients enrolled in PROTECT VIII, 121 patients aged 15 to 67 years (median age, 40 years) at the data cutoff (January 2018) continued in the extension with either on-demand treatment (n=14) or prophylaxis (n=107). At the time of analysis, patients had spent a median of 3.9 years (range, 297–1965 days) in the study since enrollment, with a median of 223 (range, 23–563) exposure days. Median (quartile [Q] 1; Q3) ABR for total bleeds during the extension study was 34.1 (20.3; 36.6) for on-demand patients and 1.6 (0.3; 4.6) for prophylaxis patients. Median (Q1; Q3) ABR for joint bleeds was 0.9 (0; 3.3) for prophylaxis patients during the extension. Median (Q1; Q3) ABR for total bleeds during the extension was similar for patients receiving prophylaxis twice weekly (1.7 [0.8; 3.6]; n=23), every 5 days (1.2 [0; 4.6]; n=33), and every 7 days (0.7 [0; 1.6]; n=23); among patients who switched prophylaxis frequency during the extension (n=28), total ABR was 3.1 (1.2; 6.2). Compared with the main study, ABR during the extension was further reduced in patients who remained in their treatment arm, including patients receiving prophylaxis every 7 days (median [Q1; Q3] main study ABR for total bleeds, 0.96 [0; 4.3]) . Of patients receiving prophylaxis, 20.6% had zero bleeds during the extension. No safety issues were identified.
Conclusions:
Good bleeding control was maintained with BAY 94-9027 prophylaxis with extended intervals of every 5 days and every 7 days throughout the PROTECT VIII extension study for up to >5 years.