Objective:
Recombinant factor IX Fc fusion protein (rFIXFc) is an extended half-life therapy approved for the treatment of children and adults with hemophilia B. B-LONG parent (NCT01027364) and B-YOND extension (NCT01425723) Phase 3 studies evaluated the safety and efficacy of rFIXFc in prevention and treatment of bleeding in previously treated subjects with severe hemophilia B. This analysis evaluated clinical outcomes for over 3 years in a subgroup aged ≥50 years using B-LONG and B-YOND interim data cut 2.
Methods:
Subjects were assigned to one of the following treatment regimens: weekly prophylaxis (WP; 20–100 IU/kg every 7 days), individualized interval prophylaxis (IP; 100 IU/kg every 8–16 days), modified prophylaxis (MP-tailored dosing if IP and WP were suboptimal), and episodic treatment (ET; on-demand dosage dependent on type and severity of bleeding episode). In B-YOND, subjects could change treatment groups at any time and may appear in more than one treatment regimen. For this subgroup analysis outcomes included inhibitor development, the annualized bleeding rate (ABR), ABRs for subjects with target joints and target joint resolution, hemophilia quality of life questionnaire for adults (Hem-A-QoL), cumulative exposure, and factor consumption.
Summary:
Overall, 26 subjects ≥50 years of age (median [range], 56 [50–71] years) in B-LONG and/or B-YOND received rFIXFc (WP, n = 13; IP, n = 7; MP, n = 3; ET, n = 8). Baseline median (interquartile range [IQR]) ABR was 1 (0–5) and 20 (12–27) for subjects who received prophylaxis and on-demand treatment regimens, respectively. No subjects developed inhibitors. On-treatment overall ABRs (median [IQR]; with n ≥5) were 2.13 (1.16–4.35; WP), 1.14 (0.48–2.64; IP), and 12.83 (8.96–20.59; ET). On-treatment target joint ABR (median [IQR]; with n ≥5) was 3.17 (1.16–4.35; WP, n=9). All 19 target joints resolved with prophylactic treatment. Mean (standard deviation) total Hem-A-QoL score changed by –3.9 (10) points from baseline to last visit for 9 subjects always on prophylactic treatment during the parent and extension studies. Subjects had a median (IQR) of 3.42 (0.98–4.31) years of treatment with rFIXFc and 90 (44.0–198) cumulative rFIXFc exposure days. Factor consumption remained stable.
Conclusions:
In subjects ≥50 years of age with severe hemophilia B, these data from over 3 years of rFIXFc prophylaxis demonstrated sustained bleed control and target joint resolution while maintaining consistent factor consumption. Results are consistent with the overall study population, suggesting that rFIXFc treatment provides long-term clinical benefits for individuals with severe hemophilia B, irrespective of age and presence of target joints.