Clinical Outcomes in Children with Hemophilia B Treated Long Term with rFIXFc: Interim Results of the B-YOND Extension Study

Abstract

Background: Early prophylactic replacement of coagulation factor IX (FIX) improves clinical outcomes in children with hemophilia B; however, frequent intravenous infusions (2-3 times/week) are often required due to the short half-life of conventional FIX products. Recombinant FIX Fc fusion protein (rFIXFc), which is produced in a human cell line, binds the neonatal Fc receptor and utilizes the natural IgG recycling pathway to prolong the half-life of FIX.The phase 3 Kids B-LONG study (NCT01425723) demonstrated the safety, efficacy and prolonged half-life of once weekly recombinant factor IX Fc fusion protein (rFIXFc) in children aged Methods: Upon completing Kids B-LONG, eligible subjects could participate in one of 3 treatment groups in B-YOND: weekly prophylaxis (WP; 20-100 IU/kg every 7 days), individualized prophylaxis (IP; 100 IU/kg every 8-16 days), or modified prophylaxis (MP; for subjects not achieving optimal prophylactic dosing with individualized or weekly prophylaxis). Subjects could change treatment groups at the start of or at any time during the study; for efficacy analyses, data were summarized according to the treatment group in which they participated, for the time period they were in that treatment group. The primary endpoint was development of inhibitors (neutralizing antibodies; confirmed at a central laboratory per Nijmegen-modified Bethesda assay result ≥0.6 BU/mL observed twice within 2-4 weeks). Secondary outcomes included incidence of adverse events (AEs), annualized bleeding rate (ABR), and rFIXFc exposure days (EDs). Post hoc analyses of subjects9 prophylactic dose and dosing interval were performed to evaluate the stability of prophylactic dosing regimens over time. Results: At the time of the B-YOND interim data cut (17 October 2014), 23 subjects had completed Kids B-LONG; all enrolled in B-YOND ( Conclusions: These data confirm the long-term safety of rFIXFc and the maintenance of a low ABR in children treated with extended-interval prophylaxis. Disclosures Kulkarni:Kedrion: Membership on an entity9s Board of Directors or advisory committees; Pfizer: Membership on an entity9s Board of Directors or advisory committees; Novo Nordisk: Membership on an entity9s Board of Directors or advisory committees, Research Funding, Speakers Bureau; Bayer: Membership on an entity9s Board of Directors or advisory committees, Research Funding; Baxter: Membership on an entity9s Board of Directors or advisory committees, Research Funding; Biogen: Research Funding, Speakers Bureau; BPL: Membership on an entity9s Board of Directors or advisory committees. Nolan:Biogen and Sobi: Research Funding. Fischer:Baxalta/Baxter, Bayer, Pfizer, Novo Nordisk, and Biogen: Consultancy; Baxalta/Baxter, Bayer, Pfizer, and Novo Nordisk: Research Funding; Baxalta/Baxter, Bayer, Pfizer, Novo Nordisk, CSL Behring, and Octopharma: Speakers Bureau. Perry:Biogen: Consultancy, Honoraria; Novo Nordisk: Consultancy, Membership on an entity9s Board of Directors or advisory committees. Barnes:Bayer, Novo Nordisk, and Pfizer: Research Funding; Bayer, Baxter, and Novo Nordisk: Membership on an entity9s Board of Directors or advisory committees. Yuan:Biogen: Employment, Equity Ownership. Ramirez-Santiago:Biogen: Employment, Equity Ownership. Pierce:Biogen: Equity Ownership, Other: Former employee. Mei:Biogen: Employment, Equity Ownership.