Post hoc longitudinal assessment of the efficacy and safety of recombinant factor IX Fc fusion protein in hemophilia B

• Published in: Blood advances Vol. 7; no. 13; pp. 3049 - 3057
• Main Authors: Shapiro, Amy D., Kulkarni, Roshni, Ragni, Margaret V., Chambost, Hervé, Mahlangu, Johnny, Oldenburg, Johannes, Nolan, Beatrice, Ozelo, Margareth C., Foster, Meredith C., Willemze, Annemieke, Barnowski, Christopher, Jain, Nisha, Winding, Bent, Dumont, Jennifer, Lethagen, Stefan, Barnes, Chris, Pasi, K. John
• Format: Journal Article
• Language: English
• Published: United States Elsevier Inc 11.07.2023; The American Society of Hematology
• Subjects: Clinical Trials and Observations; Factor IX - adverse effects; Factor IX - therapeutic use; Hemophilia A - drug therapy; Hemophilia B - complications; Hemophilia B - drug therapy; Hemorrhage - chemically induced; Humans; Immunoglobulin Fc Fragments - adverse effects; Immunoglobulin Fc Fragments - therapeutic use; Life Sciences; Recombinant Fusion Proteins - adverse effects; Recombinant Fusion Proteins - therapeutic use
• ISSN: 2473-9529; 2473-9537; 2473-9537
• DOI: 10.1182/bloodadvances.2022009230

•Pooled longitudinal efficacy and safety data for rFIXFc demonstrates sustained benefits in hemophilia B.•All evaluable target joints resolved during treatment, and no recurrence was reported in most (90%) baseline target joints during follow-up. [Display omitted] Long-term efficacy and safety of the extended half-life recombinant factor IX Fc fusion protein (rFIXFc) has been established among previously treated patients with severe hemophilia B in 2 phase 3 trials (B-LONG [#NCT01027364] and Kids B-LONG [#NCT01440946]) and a long-term extension study (B-YOND [#NCT01425723]). In this study, we report post hoc analyses of pooled longitudinal data for up to 6.5 years for rFIXFc prophylaxis. In the B-LONG study, subjects ≥12 years received weekly dose-adjusted prophylaxis (WP; starting dose, 50 IU/kg), individualized interval-adjusted prophylaxis (IP; initially, 100 IU/kg every 10 days), or on-demand dosing. In the Kids B-LONG study, subjects <12 years received 50 to 60 IU/kg every 7 days, adjusted as needed. In the B-YOND study, subjects received WP (20-100 IU/kg every 7 days), IP (100 IU/kg every 8-16 days), modified prophylaxis, or on-demand dosing; switching between treatment groups was permitted. A total of 123 subjects from B-LONG and 30 from Kids B-LONG study were included, of whom 93 and 27, respectively, enrolled in the B-YOND study. The median cumulative duration of treatment was 3.63 years (range, 0.003-6.48 years) in B-LONG/B-YOND and 2.88 years (range, 0.30-4.80 years) in Kids B-LONG/B-YOND group. Annualized bleed rates (ABRs) remained low, annualized factor consumption remained stable, and adherence remained high throughout treatment. Low ABRs were also maintained in subjects with dosing intervals ≥14 days or with target joints at baseline. Complete resolution of evaluable target joints and no recurrence in 90.2% of baseline target joints during follow-up were observed. rFIXFc prophylaxis was associated with sustained clinical benefits, including long-term bleed prevention and target joint resolution, for severe hemophilia B.