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

Abstract

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.

• Authors: K John Pasi, Kathelijn Fischer, Margaret Ragni, Beatrice Nolan, David J Perry, Roshni Kulkarni, Margareth Ozelo, Johnny Mahlangu, Amy D Shapiro, Ross I Baker, Carolyn M Bennett, Christopher Barnes, Johannes Oldenburg, Tadashi Matsushita, Huixing Yuan, Alejandra Ramirez-Santiago, Glenn F Pierce, Geoffrey Allen, Baisong Mei
• Journal: Thrombosis and haemostasis (Thromb Haemost) Vol. 117 Issue 3 Pg. 508-518 (02 28 2017) ISSN: 2567-689X [Electronic] Germany
• PMID: 28004057 (Publication Type: Clinical Trial, Comparative Study, Journal Article, Research Support, Non-U.S. Gov't)

Chemical References

• Antibodies, Neutralizing
• Coagulants
• Immunoglobulin Fc Fragments
• Recombinant Fusion Proteins
• factor IX Fc fusion protein
• Factor IX

Topics

• Adolescent
• Adult
• Antibodies, Neutralizing (blood)
• Child
• Coagulants (administration & dosage, adverse effects)
• Drug Administration Schedule
• Factor IX (administration & dosage, adverse effects, immunology)
• Hemophilia B (blood, diagnosis, drug therapy)
• Hemorrhage (blood, prevention & control)
• Hemostasis (drug effects)
• Humans
• Immunoglobulin Fc Fragments (administration & dosage, adverse effects, immunology)
• Male
• Middle Aged
• Recombinant Fusion Proteins (administration & dosage, adverse effects, immunology)
• Risk Factors
• Time Factors
• Treatment Outcome
• Young Adult