Post hoc longitudinal assessment of the efficacy and safety of recombinant factor IX Fc fusion protein in hemophilia B
- PMID: 36848635
- PMCID: PMC10331408
- DOI: 10.1182/bloodadvances.2022009230
Post hoc longitudinal assessment of the efficacy and safety of recombinant factor IX Fc fusion protein in hemophilia B
Abstract
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.
© 2023 by The American Society of Hematology. Licensed under Creative Commons Attribution-NonCommercial-NoDerivatives 4.0 International (CC BY-NC-ND 4.0), permitting only noncommercial, nonderivative use with attribution. All other rights reserved.
Conflict of interest statement
Conflict-of-interest disclosure: A.D.S. has participated in advisory board meetings for Shire, Novo Nordisk, Bioverativ (a Sanofi company), and Genentech; undertaken consultancy work for Prometic Life Sciences, Kedrion Biopharma, Sangamo Biosciences, Bio Products Laboratory; and received research funding from Shire, Novo Nordisk, Bioverativ, Genentech, Prometic Life Sciences, Daiichi Sankyo, Opko Biologics, Octapharma, BioMarin, and the International Network of Pediatric Hemophilia: Bayer Healthcare. R.K. has received honoraria from Bioverativ, Bayer, Novo Nordisk, Shire, Octapharma, Kedrion, Genentech, and BP; received research funding from Bioverativ, Bayer, Novo Nordisk, and Shire; and participated in advisory committees for Octapharma, Kedrion, Genentech, and BPL. M.V.R. has received research funding from Alnylam, BioMarin, Bioverativ, CSL Behring, Novo Nordisk, OPKO Biologics, Sangamo, and Spark and has participated in advisory boards for Alnylam, Bayer, BioMarin, Bioverativ, MOGAM (Green Cross Corporation), and Spark. H.C. has received honoraria from BioMarin, LFB, NovoNordisk, Octapharma, Pfizer, Roche/Chugai, and Sobi for boards bureau and presentations in symposia and is a principal investigator in clinical studies promoted by Baxalta/Shire, BioMarin, Octapharma, Pfizer, Roche, and Sanofi/Sobi. J.M. has provided consultancy for Catalyst Biosciences, Chugai, CSL Behring, Novo Nordisk, LFB, Roche, Shire, and Spark; received research funding from BioMarin, Catalyst Biosciences, CSL Behring, Novo Nordisk, Roche, Shire, and Sobi; and participated in a speaker bureau for BioMarin, CSL Behring, Novo Nordisk, Roche, Sanofi, Shire, and Sobi. J.O. has received honoraria and research funding from Bayer, Biogen, Biotest, Chugai, CSL Behring, Grifols, Novo Nordisk, Octapharma, Pfizer, Roche, Shire, and Sobi. B.N. has received research funding from Bayer, CSL Behring, Sobi, and Bioverativ. M.C.O. has received research funding and honoraria from Shire, Novo Nordisk, Bioverativ, BioMarin, Roche, and Pfizer. A.W., M.C.F., and J.D. are employees of and hold an equity interest in Sanofi. N.J. and C. Barnowski are former employees of Sanofi, and C. Barnowski holds an equity interest in Sanofi. B.W. is a former employee of Sobi. S.L. is an employee of and holds an equity interest in Sobi. K.J.P. has received honoraria from BioMarin, Alynylam, Bioverativ (a Sanofi company), Sobi, Octapharma, Catalyst, and ApcinteX; received research funding from BioMarin, Alnylam, and Bioverativ; and participated in a speakers bureau for Pfizer, Bayer, Shire, and Novo Nordisk. C. Barnes declares no competing financial interests.
The current affiliation for A.W. is Sanofi, Amsterdam, The Netherlands.
The current affiliation for C. Barnowski is Vertex Pharmaceuticals, Boston, MA.
The current affiliation for N.J. is Takeda, Cambridge, MA.
The current affiliation for B.W. is Ascendis Pharma, Copenhagen, Denmark.
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