Long-Term Use of Coagulation Factor IX (Recombinant) Albumin Fusion Protein (rIX-FP) in Previously Treated Patients with Hemophilia B in the Prolong-9FP Program

A fusion protein genetically linking recombinant human coagulation FIX with recombinant human albumin (rIX-FP) has been developed with an improved PK profile, improving hemophilia B treatment by allowing less frequent dosing than required with standard plasma-derived (pd) and recombinant (r) FIX products. The PROLONG-9FP clinical program has evaluated the use of rIX-FP for prophylaxis and on-demand treatment of bleeding in patients with severe hemophilia B. The clinical program is comprised of 5 clinical studies, including four completed studies (a Phase I pharmacokinetic (PK) study, a Phase II study, and two Phase III studies in adults and children), and an ongoing extension study, which includes previously untreated patients. Over 100 subjects from 42 hemophilia treatment centers in 12 countries have participated in the PROLONG-9FP clinical program. Here, we report on the long-term safety and efficacy of rIX-FP in 15 subjects who have continuously participated in 3 clinical studies (Phase II, Phase III and the on-going Phase III extension studies) over a period of 4 years.

Subjects began either weekly prophylaxis treatment or on-demand treatment with rIX-FP in the Phase II 2004 study, and continued that treatment regimen in the Phase III 3001 study. The Phase III global study evaluated safety and efficacy of rIX-FP for prophylaxis treatment (PT) of every 7-, 10- and 14-days and on-demand treatment (ODT) of bleeding episodes. Subjects in the on-demand arm received only ODT for 6 months and then switched to 7-day PT. Subjects in the prophylaxis arm received 7-day PT for 6 months, and eligible subjects switched to 10- or 14-day PT interval. Upon completion of the 3001 study, subjects entered the on-going extension study 3003 and either continued the treatment regimen or switched to a longer prophylaxis interval of 10-, 14- or 21-days. Within subject comparisons of the annualized spontaneous bleeding rates (AsBR), total ABR over time and other efficacy parameters between regimens will be presented.

Long-term use of rIX-FP is safe and well-tolerated. No subjects developed inhibitors to FIX or antibodies to rIX-FP during the 4 year treatment period, with a mean of 180 exposure days (EDs) for PT subjects and 125 EDs for ODT subjects. ABR decreased over time with rIX-FP prophylaxis, and longer treatment intervals were possible with no increase in consumption.