title: 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.forename: K John
authors.initials: KJ
authors.lastname: Pasi
authors.forename: Kathelijn
authors.initials: K
authors.lastname: Fischer
authors.forename: Margaret
authors.initials: M
authors.lastname: Ragni
authors.forename: Beatrice
authors.initials: B
authors.lastname: Nolan
authors.forename: David J
authors.initials: DJ
authors.lastname: Perry
authors.forename: Roshni
authors.initials: R
authors.lastname: Kulkarni
authors.forename: Margareth
authors.initials: M
authors.lastname: Ozelo
authors.forename: Johnny
authors.initials: J
authors.lastname: Mahlangu
authors.forename: Amy D
authors.initials: AD
authors.lastname: Shapiro
authors.forename: Ross I
authors.initials: RI
authors.lastname: Baker
authors.forename: Carolyn M
authors.initials: CM
authors.lastname: Bennett
authors.forename: Christopher
authors.initials: C
authors.lastname: Barnes
authors.forename: Johannes
authors.initials: J
authors.lastname: Oldenburg
authors.forename: Tadashi
authors.initials: T
authors.lastname: Matsushita
authors.forename: Huixing
authors.initials: H
authors.lastname: Yuan
authors.forename: Alejandra
authors.initials: A
authors.lastname: Ramirez-Santiago
authors.forename: Glenn F
authors.initials: GF
authors.lastname: Pierce
authors.forename: Geoffrey
authors.initials: G
authors.lastname: Allen
authors.affiliation: Baisong Mei, Biogen, 225 Binney St, Cambridge, MA 02142, USA, Tel.: +1 781 464 3269, Fax: +1 888 679 1018, E-mail: baisong.mei@biogen.com.
authors.forename: Baisong
authors.initials: B
authors.lastname: Mei
mesh_terms: D000293:Adolescent; D000328:Adult; D057134:Antibodies, Neutralizing / Q000097:blood; D002648:Child; D003029:Coagulants / Q000008:administration & dosage* / Q000009:adverse effects; D004334:Drug Administration Schedule; D005164:Factor IX / Q000008:administration & dosage* / Q000009:adverse effects / Q000276:immunology; D002836:Hemophilia B / Q000097:blood / Q000175:diagnosis / Q000188:drug therapy*; D006470:Hemorrhage / Q000097:blood / Q000517:prevention & control*; D006487:Hemostasis / Q000187:drug effects*; D006801:Humans; D007141:Immunoglobulin Fc Fragments / Q000008:administration & dosage* / Q000009:adverse effects / Q000276:immunology; D008297:Male; D008875:Middle Aged; D011993:Recombinant Fusion Proteins / Q000008:administration & dosage* / Q000009:adverse effects / Q000276:immunology; D012307:Risk Factors; D013997:Time Factors; D016896:Treatment Outcome; D055815:Young Adult
chemical_list: D057134:Antibodies, Neutralizing; D003029:Coagulants; D007141:Immunoglobulin Fc Fragments; D011993:Recombinant Fusion Proteins; C000599709:factor IX Fc fusion protein; D005164:Factor IX
keywords: Factor IX; haemophilia; prophylaxis; recombinant fusion proteins