In individuals with severe hemophilia B, the use of recombinant factor IX Fc fusion protein (rFIXFc) was associated with sustained clinical benefits, including complete resolution of target joints and long-term bleed prevention, according to findings from a post hoc analysis of pooled longitudinal data published in Blood Advances.
In patients with severe hemophilia B, the standard-of-care therapy for long-term management of the disease is coagulation FIX. Recurrent, spontaneous bleeds into joints are reported among those with the disease, leading to hemophilic arthropathy, along with resultant impaired functionality, chronic pain, and decreased quality of life.
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The current post hoc evaluation of longitudinal efficacy and safety data on extended half-life prophylactic rFIXFc regimens were derived from the following clinical trials, which were conducted among previously treated patients with severe hemophilia B:
- Phase 3 B-LONG trial;
- Phase 3 Kids B-LONG trial; and
- Global long-term B-YOND extension study
The B-LONG and Kids B-LONG trials were both multicenter, open-label, nonrandomized studies that evaluated the efficacy, safety, and pharmacokinetics of rFIXFc in previously treated participants with severe hemophilia B (≤2 IU/dL) who had no history of inhibitors.
In B-LONG, participants 12 years of age and older were receiving weekly dose-adjusted prophylaxis (WP; starting dose,
50 IU/kg), individualized interval-adjusted prophylaxis (IP; 100 IU/kg every 10 days), or on-demand dosing, or had a history of 8 or more episodes of bleeding in the year prior to study enrollment. These patients needed to have accumulated 100 or more exposure days to FIX replacement.
In Kids B-LONG, participants 12 years of age and younger were receiving once-weekly prophylactic rFIXFc (starting dose, 50-60 IU/kg) and needed to have accumulated 50 or more exposure days to replacement FIX.
B-YOND enrolled eligible patients from B-LONG and Kids B-LONG. Participants received WP (20-100 IU/kg every
7 days), IP (100 IU/kg every 8-16 days), modified prophylaxis, or on-demand dosing. B-YOND participants were allowed to switch treatments.
One hundred twenty-three participants were enrolled in B-LONG and 30 participants in Kids B-LONG. Among these individuals, 93 from B-LONG and 27 from Kids B-LONG were enrolled in B-YOND.
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In the pooled analysis from B-LONG/B-YOND, the median duration of treatment was 3.63 years (range, 0.003-6.48 years). The number of exposure days from B-LONG initiation to conclusion of follow-up was 165 days (range, 1-528 days). Respective values in the Kids B-LONG/B-YOND pooled analysis were 2.88 years (range, 0.30-4.80 years) and 166 days (range, 18-256 days).
Study results showed that annualized bleeding rates (ABRs) remained low in all patient age-groups in those who received 1 to 5 years (1-4 years for participants from Kids B-LONG) of prophylactic rFIXFc therapy. In participants with target joints at baseline or dosing intervals of 14 days or more, low ABRs also were retained. During follow-up, no recurrence was observed in 90.2% of baseline target joints.
“Overall, rFIXFc prophylaxis offers individuals with hemophilia B the opportunity for personalized single-agent protection with the flexibility to target desired trough levels to meet patient needs,” the researchers concluded.
Shapiro AD, Kulkarni RD, Ragni MV, et al. Post hoc longitudinal assessment of efficacy and safety of recombinant factor IX Fc fusion protein in hemophilia B. Blood Adv. Published online February 23, 2023. doi:10.1182/bloodadvances.2022009230