Long-term Safety and Efficacy of rIX-FP in Patients with Hemophilia B: Intermediate Results from a Phase IIIb Extension Study

Scientific Research Question: To investigate the long-term safety and efficacy of rIX-FP in previously treated patients (PTPs) over approximately 3 years.

Methodology: At the start of the study, PTPs received routine prophylaxis with rIX-FP at 35-50 IU/kg every 7 days, or 50-75 IU/kg every 10 or 14 days. During the extension study, PTPs who were well controlled could extend their dosing interval to every 10 or 14 days. Adult patients ≥18 years of age could switch to a 21-day regimen at a dose of 100 IU/kg if they were well controlled on a 14-day regimen. The primary endpoint was the number of patients who developed inhibitors against FIX. Secondary endpoints included annualized spontaneous bleeding rate (AsBR) and adverse events.

Findings: As of March 2017 (interim datacut), 83 PTPs (n = 59 and n = 24, ≥12 and < 12 years, respectively) had entered the study (mean time on study 29.8 months). In patients ≥12 years, over 79% switched from weekly to 10 (n = 12), 14 (n = 26) or 21-day intervals (n = 9). Two patients starting 21-day dosing switched back to the 14 day interval to reduce their bleeding frequency. 25% of patients < 12 were on the extended prophylaxis intervals of once every 10 (n = 1) or 14 days (n = 5). In adults, median (Q1, Q3) AsBR for 7, 10, 14 and 21 day regimens was 0.33 (0.00, 2.39), 0 (0.00, 0.68), 0.26 (0.00, 1.54) and 0 (0.00, 0.45), respectively. In pediatrics, median AsBR for 7, 10 and 14 day regimens was 0 (0.00, 0.59), 0 (0.00, 3.06) and 0.75 (0.00, 2.86), respectively. Median number of exposure days (EDs) was 165 and 77 (92.8%) subjects have achieved 100 EDs to rIX-FP; none have developed inhibitors or antibodies to rIX-FP.

Conclusions: Long-term efficacy and tolerability of prophylaxis with rIX-FP have been demonstrated. rIX-FP allows extended treatment intervals of 21 days in selected adults, and 10 and 14 days in selected children.