Objective:
BAY 94-9027 is an extended–half-life recombinant factor VIII (FVIII) product. In the PROTECT VIII study, BAY 94-9027 provided effective protection against bleeds and was well tolerated with twice-weekly, every-5-day, and every-7-day prophylaxis in patients with severe hemophilia A. We report interim safety data from the PROTECT VIII extension study evaluating long-term outcomes in patients using BAY 94-9027 prophylaxis for >5 years .
Methods:
Previously treated patients aged 12 to 65 years with severe hemophilia A were enrolled in PROTECT VIII, in which they received BAY 94-9027 for 36 weeks on demand or as twice-weekly (30–40 IU/kg), every-5-day (45–60 IU/kg), or every-7-day (60 IU/kg) prophylaxis. Patients could subsequently participate in an extension study with the same or a different regimen. Adverse events (AEs), anti-PEG antibodies, inhibitor development, renal safety, and plasma PEG levels were evaluated during the extension phase.
Summary:
One hundred twenty-one of 134 patients from PROTECT VIII continued in the extension study receiving BAY 94-9027 either on demand (n=14) or as prophylaxis (n=107). At data cutoff (January 2018), patients aged 15 to 67 years at time of analysis (median age, 40 y) had a median (range) of 1420 (297–1965) days in the trial since enrollment and a median (range) of 223 (23–563) exposure days . Prophylaxis patients were treated either twice weekly (n=23), every 5 days (n=33), every 7 days (n=23), or switched frequency during the extension (n=28) . Overall, 9 patients (7.4%) experienced treatment-related AEs during the extension classified as either mild (n=4), moderate (n=4), or severe (n=1) . Two patients (1.7%) experienced 3 SAEs considered to be treatment-related (elevated liver function tests in a patient with hepatitis C ; 2 incidences of back pain); these 2 patients discontinued the study. Transient low-titer anti-PEG antibodies were detected at a single visit in 8 patients but were not associated with clinical events. No patients developed FVIII inhibitors or had sustained levels of detectable PEG in plasma . No specific changes in renal parameters were observed.
Conclusions:
During the ongoing PROTECT VIII extension, BAY 94-9027 prophylaxis was well tolerated for >5 years, and no patients developed FVIII inhibitors.