Long-term use of recombinant fusion protein linking coagulation factor IX with albumin (rIX-FP) in previously treated patients with hemophilia B
S. Halimeh1, A. Lubetsky2, U. Martinowitz2, T. Lissitchkov3, A. Veldman4, E. Santagostino5 (1Duisberg, Germany, 2Tel Hashomer, Israel, 3Sofia, Bulgaria, 4Marburg, Germany, 5Milan, Italy)
Bleeding disorders, coagulation and fibrinolytic factors
Time: 17:15 - 18:15
Objective: rIX-FP is a fusion protein genetically linking recombinant human coagulation factor IX with recombinant human albumin. It was designed specifically to have an improved pharmacokinetic profile compared with standard factor IX products to allow less frequent dosing.
Methods: The PROLONG-9FP clinical program evaluated the safety and efficacy of rIX-FP both as prophylactic therapy and on-demand treatment (ODT). The 5 clinical studies in the trial program enrolled 100 subjects from 42 hemophilia treatment centers in 12 countries. In this analysis, patients (12–65 years) who had continuously participated in 3 rIX-FP clinical trials over a 4-year period were included. Patients were initially recruited into the Phase II trial and received either ODT or weekly prophylaxis. Patients continued into the Phase III trial, receiving the same treatment for 6 months, after which those receiving ODT switched to weekly prophylaxis, while those receiving weekly prophylaxis were eligible to extend their treatment interval to once every 10 or 14 days. Patients continued into the Phase IIIb extension study where they received prophylaxis every 7, 10, 14 or 21 days.
Results: Of the 15 patients included in the analysis, 4 started with ODT and switched to prophylaxis in the Phase III study; the remaining patients received prophylaxis in all studies. Patients had a median (range) of 4.2 (3.2–4.3) years on rIX-FP. For those on prophylaxis, median (range) number of exposure days was 199 (144–232); for those initiating ODT corresponding figures were 130 (121–137). With 7-day prophylaxis, mean annualized bleeding rate (ABR) fell from 3.10 in Phase II to 1.27 in Phase III. This decrease in ABR over time was achieved with constant monthly consumption of rIX-FP (240–250 IU/kg). With both 7- and 14-day regimens, there was a decrease in spontaneous ABR over time. Monthly consumption of rIX-FP decreased with longer prophylaxis interval: 7-day, 245 IU/kg; 10-day, 220 IU/kg; 14-day, 158 IU/kg. No patients developed inhibitors or antibodies to rIX-FP during the treatment period.
Conclusion: Long-term use of rIX-FP was well tolerated; prophylactic efficacy was maintained throughout the 4-year treatment period and resulted in a decrease in ABR over time. Longer treatment intervals were possible with no increase in consumption