Objective:
BAY 94-9027 is an extended–half-life recombinant factor VIII (FVIII) product. In the PROTECT VIII Kids trial, BAY 94-9027 was efficacious for the prevention and treatment of bleeding episodes in previously treated children with severe hemophilia A. We report interim long-term efficacy and safety data from the PROTECT VIII Kids extension study.
Methods:
In PROTECT VIII Kids, previously treated patients (PTPs) aged <12 years with severe hemophilia A received BAY 94-9027 prophylaxis twice weekly (25‒60 IU/kg), every 5 days (45‒60 IU/kg), or every 7 days (60 IU/kg). Patients completing ≥50 exposure days (EDs) and ≥6 months in the main study or a 12-week safety substudy (part 2) that enrolled PTPs aged <6 years could continue in the optional extension for an additional ≥50 EDs.
Summary:
Fifty-nine of 73 patients treated with BAY 94-9027 in PROTECT VIII Kids (main study or part 2) continued in the extension (median [range] age at enrollment in the main study, 5.0 [2–11] years). At data cutoff (January 2018), patients had a median (range) of 1456 (351–1665) days in the trial (main study or part 2 plus extension). Patients in the extension received prophylaxis twice weekly (n=20), every 5 days (n=20), every 7 days (n=8), or switched prophylaxis frequency during the extension (variable frequency; n=11). Median (range) dose/infusion was 52.1 (19–62) IU/kg. Median annualized bleeding rate (ABR) for total bleeds was 1.8 for all patients and 0.8, 1.1, 2.1, and 3.2 for those treated twice weekly, every 5 days, every 7 days, or with varying frequency, respectively. Median ABR for joint bleeds in all patients was 0.7. During the extension, 3 patients (5.1%) experienced treatment-related adverse events (AEs) classified as mild (n=1), moderate (n=1), or severe (n=1). One patient discontinued because of a serious AE that was not related to treatment. No confirmed FVIII inhibitors or anti-PEG antibodies were observed; no patients had sustained levels of detectable PEG in plasma.
Conclusions:
Long-term treatment (up to ~4.5 years) with BAY 94-9027 prophylaxis was efficacious and well tolerated in previously treated pediatric patients with severe hemophilia A.