Objective:
Safety and efficacy of long-lasting recombinant factor IX Fc fusion protein (rFIXFc), currently being developed to provide extended protection from bleeding in hemophilia B patients, were demonstrated in the phase 3 B-LONG study, where a half-life of 82 hours was observed. Here we describe how patients in B-LONG who were on prophylaxis with FIX prior to study entry were treated with rFIXFc and their clinical outcomes during B- LONG.
Methods:
Patients who were on prophylaxis with FIX prior to study entry were identified. Patients’ self-reported FIX dosing regimen and bleeding rates pre-study were compared to their rFIXFc dosing regimen and annualized bleeding rates on study. All patients were monitored for safety, including inhibitor formation.
Summary:
Of 123 patients enrolled, 48 received prophylaxis with FIX pre-study: 33 in Arm 1 (weekly prophylaxis: rFIXFc 50 IU/kg once weekly, dose adjusted based on FIX activity); 15 in Arm 2 (individualized dosing interval: rFIXFc 100 IU/kg every 10 days, interval adjusted based on FIX activity). The most common pre-study dosing intervals were twice weekly (67%), thrice weekly (18%), and once weekly (13%). The 21 patients in Arm 1 reporting twice weekly dosing pre-study had a median pre-study dose of 36.4 IU/kg per injection (total weekly dose: 72.7 IU/kg); in their last 3 months on-study, these patients received a median dose of 36.4 IU/kg rFIXFc once weekly. The 9 patients in Arm 2 reporting twice-weekly dosing pre-study had a median pre-study dose of 37.9 IU/kg per injection (total weekly dose: 75.9 IU/kg); in their last 3 months on-study, these patients received a median dose of 103 IU/kg rFIXFc at a median interval of once every 13.5 days. Overall, Arm 1 patients on prophylaxis pre-study reported a bleeding rate of 2.5 in the 12 months prior to study entry; on-study, they had an annualized bleeding rate of 2.1. Arm 2 patients on prophylaxis pre-study reported a bleeding rate of 2.0 in the 12 months prior to study entry; on-study they had an annualized bleeding rate of 0.0. Based on population pharmacokinetic modelling, approximately 95% of people with hemophilia B receiving 50 IU/kg rFIXFc once weekly were predicted to maintain FIX trough levels above 1% at all times. In the B-LONG study, rFIXFc was well tolerated and no inhibitor development was detected.
Conclusions:
Prophylaxis with rFIXFc may provide patients who are currently on prophylaxis the option for dosing every 1-2 weeks with low bleeding rates.