Long acting recombinant coagulation factor IX albumin fusion protein (rIX-FP) in hemophilia B: results of a phase 3 trial

Elena Santagostino, Uri Martinowitz, Toshko Lissitchkov, Brigitte Pan-Petesch, Hideji Hanabusa, Johannes Oldenburg, Lisa Boggio, Claude Negrier, Ingrid Pabinger, Mario von Depka Prondzinski, Carmen Altisent, Giancarlo Castaman, Koji Yamamoto, Maria-Teresa Álvarez-Roman, Christine Voigt, Nicole Blackman, Iris Jacobs

Key points

  • rIX-FP maintains mean trough of 20 and 12 IU/dL FIX activity with 40 IU/kg weekly and 75 IU/kg every 2 weeks prophylaxis, respectively.

  • Weekly and 14-day prophylaxis regimens with rIX-FP were well tolerated and provided low bleeding rates and target joint improvement.


A global Phase 3 study evaluated the pharmacokinetics, efficacy and safety of recombinant fusion protein linking coagulation factor IX with albumin (rIX-FP) in 63 previously treated male patients (12-61 years) with severe hemophilia B (FIX activity ≤ 2%). The study included 2 groups: Group 1 patients received routine prophylaxis once every 7 days for 26 weeks, followed by either 7-, 10- or 14-day prophylaxis regimen for a mean of 50, 38, or 51 weeks, respectively; Group 2 patients received on-demand treatment for bleeding episodes for 26 weeks and then switched to a 7 day prophylaxis regimen for a mean of 45 weeks. The mean terminal half-life of rIX-FP was 102 hours, 4.3-fold longer than previous factor IX (FIX) treatment. Patients maintained a mean trough of 20 and 12 IU/dL FIX activity on prophylaxis with rIX-FP 40 IU/kg weekly and 75 IU/kg every 2 weeks, respectively. There was a 100% reduction in median annualized spontaneous bleeding rate (AsBR) and 100% resolution of target joints when subjects switched from on-demand to prophylaxis treatment with rIX-FP (P <0.0001). The median AsBR was 0.00 for all prophylaxis regimens. Overall, 98.6% of bleeding episodes were treated successfully, including 93.6% that were treated with a single injection. No patient developed an inhibitor and no safety concerns were identified. These results indicate that rIX-FP is safe and effective for preventing and treating bleeding episodes in patients with hemophilia B at dosing regimens of 40 IU/kg weekly and 75 IU/kg every 2 weeks. (NCT0101496274)

  • Submitted September 10, 2015.
  • Accepted December 21, 2015.