Long-term safety and efficacy of extended-interval prophylaxis with recombinant factor IX Fc fusion protein (rFIXFc) in subjects with haemophilia B

• Published in: Thrombosis and haemostasis Vol. 117; no. 3; p. 508
• Main Authors: Pasi, K John, Fischer, Kathelijn, Ragni, Margaret, Nolan, Beatrice, Perry, David J, Kulkarni, Roshni, Ozelo, Margareth, Mahlangu, Johnny, Shapiro, Amy D, Baker, Ross I, Bennett, Carolyn M, Barnes, Christopher, Oldenburg, Johannes, Matsushita, Tadashi, Yuan, Huixing, Ramirez-Santiago, Alejandra, Pierce, Glenn F, Allen, Geoffrey, Mei, Baisong
• Format: Journal Article
• Language: English
• Published: Germany 2017
• Subjects: Adolescent; Adult; Antibodies, Neutralizing - blood; Child; Coagulants - administration & dosage; Coagulants - adverse effects; Drug Administration Schedule; Factor IX - administration & dosage; Factor IX - adverse effects; Factor IX - immunology; Hemophilia B - blood; Hemophilia B - diagnosis; Hemophilia B - drug therapy; Hemorrhage - blood; Hemorrhage - prevention & control; Hemostasis - drug effects; Humans; Immunoglobulin Fc Fragments - administration & dosage; Immunoglobulin Fc Fragments - adverse effects; Immunoglobulin Fc Fragments - immunology; Male; Middle Aged; Recombinant Fusion Proteins - administration & dosage; Recombinant Fusion Proteins - adverse effects; Recombinant Fusion Proteins - immunology; Risk Factors; Time Factors; Treatment Outcome; Young Adult; haemophilia; Factor IX; recombinant fusion proteins; prophylaxis
• ISSN: 2567-689X
• DOI: 10.1160/TH16-05-0398

The safety, efficacy, and prolonged half-life of recombinant factor IX Fc fusion protein (rFIXFc) were demonstrated in the Phase 3 B-LONG (adults/adolescents ≥12 years) and Kids B-LONG (children <12 years) studies of subjects with haemophilia B (≤2 IU/dl). Here, we report interim, long-term safety and efficacy data from B-YOND, the rFIXFc extension study. Eligible subjects who completed B-LONG or Kids B-LONG could enrol in B-YOND. There were four treatment groups: weekly prophylaxis (20-100 IU/kg every 7 days), individualised prophylaxis (100 IU/kg every 8-16 days), modified prophylaxis (further dosing personalisation to optimise prophylaxis), and episodic (on-demand) treatment. Subjects could change treatment groups at any point. Primary endpoint was inhibitor development. One hundred sixteen subjects enrolled in B-YOND. From the start of the parent studies to the B-YOND interim data cut, median duration of rFIXFc treatment was 39.5 months and 21.9 months among adults/adolescents and children, respectively; 68/93 (73.1 %) adults/adolescents and 9/23 (39.1 %) children had ≥100 cumulative rFIXFc exposure days. No inhibitors were observed. Median annualised bleeding rates (ABRs) were low in all prophylaxis regimens: weekly (≥12 years: 2.3; <6 years: 0.0; 6 to <12 years: 2.7), individualised (≥12 years: 2.3; 6 to <12 years: 2.4), and modified (≥12 years: 2.4). One or two infusions were sufficient to control 97 % (adults/adolescents) and 95 % (children) of bleeding episodes. Interim data from B-YOND are consistent with data from B-LONG and Kids B-LONG, and confirm the long-term safety of rFIXFc, absence of inhibitors, and maintenance of low ABRs with prophylactic dosing every 1 to 2 weeks.