Safety, Efficacy, and Pharmacokinetics of Recombinant Factor VIII Fc Fusion Protein (rFVIIIFc) in Previously-Treated Children with Severe Hemophilia a (Kids-ALONG)

Abstract

Background: Initiation of prophylactic factor VIII (FVIII) therapy at a young age is recommended for the prevention of bleeds and associated arthropathy in severe hemophilia A. Prophylaxis requires frequent infusions of FVIII; children in particular require more frequent infusions due to a shorter FVIII circulating half-life compared with adults. Long-acting FVIII products may allow for prophylaxis with less frequent infusions. Recombinant FVIII Fc fusion protein (rFVIIIFc) had a prolonged half-life, and yielded low annualized bleeding rates (ABR) with once- to twice-weekly prophylaxis in a phase 3 study of adults and adolescents. Aims: The Kids A-LONG study evaluated the safety, efficacy, and pharmacokinetics (PK) of rFVIIIFc in previously treated children with severe hemophilia A. Methods: Kids A-LONG was a global, multi-center, open-label, phase 3 study that enrolled males Results: Of the 71 enrolled subjects ( The median on-study dosing interval was 3.5 days, with 89% of subjects receiving rFVIIIFc twice-weekly at study end. Forty-six of 62 subjects (74%) on a prior prophylactic regimen reduced their dosing frequency with rFVIIIFc. Pre-study, 30 subjects were on Advate prophylaxis (twice-weekly, n = 6; ≥3 times/week, n = 24). At study end, 21/24 subjects (88%) previously on ≥3 infusions/week were on a regimen of twice-weekly rFVIIIFc. The median average weekly prophylactic dose on study was 88.1 IU/kg. Table 1 presents the median weekly factor consumption by age cohort among all subjects on pre-study prophylaxis and among subjects on pre-study Advate. Median (IQR) on-study ABR was 1.96 (0.00, 3.96) overall and 0.00 (0.00, 0.00) for spontaneous bleeds. In the Summary/Conclusion: In this first phase 3 study of a long-acting FVIII in previously treated pediatric subjects, rFVIIIFc prophylaxis was well-tolerated and no subjects developed inhibitors. In the majority of subjects rFVIIIFc half-life was prolonged relative to FVIII, consistent with the ~1.5-fold increase observed in adults and adolescents. With rFVIIIFc, low bleeding rates were maintained with a reduced infusion frequency compared with prior FVIII therapy, and similar overall factor consumption. Disclosures Young:Baxter: Consultancy; Biogen Idec: Consultancy, Honoraria; Kedrion: Membership on an entity9s Board of Directors or advisory committees; Novo Nordisk: Consultancy, Honoraria. Mahlangu:Amgen: Membership on an entity9s Board of Directors or advisory committees; Bayer: Membership on an entity9s Board of Directors or advisory committees, Research Funding; Biogen Idec: Research Funding, Speakers Bureau; Novo Nordisk: Membership on an entity9s Board of Directors or advisory committees, Research Funding, Speakers Bureau; Pfizer: Membership on an entity9s Board of Directors or advisory committees; Genentech: Membership on an entity9s Board of Directors or advisory committees; Biotest: Speakers Bureau. Kulkarni:Baxter: Membership on an entity9s Board of Directors or advisory committees, Research Funding; Bayer: Membership on an entity9s Board of Directors or advisory committees; Biogen Idec: Consultancy, Membership on an entity9s Board of Directors or advisory committees, Research Funding; Novo Nordisk: Honoraria, Membership on an entity9s Board of Directors or advisory committees, Research Funding; Octapharma: Research Funding; Pfizer: Membership on an entity9s Board of Directors or advisory committees. Nolan:Biogen Idec: Research Funding; Bayer: Research Funding. Liesner:Baxter: Consultancy, Membership on an entity9s Board of Directors or advisory committees; Bayer: Consultancy, Honoraria, Membership on an entity9s Board of Directors or advisory committees; CSL Behring: Membership on an entity9s Board of Directors or advisory committees; Novo Nordisk: Consultancy; Pfizer: Consultancy, Honoraria, Membership on an entity9s Board of Directors or advisory committees. Pasi:Bayer: Membership on an entity9s Board of Directors or advisory committees; BPL: Membership on an entity9s Board of Directors or advisory committees; Biogen Idec: Educational Support and Travel Grants, Educational Support and Travel Grants Other, Membership on an entity9s Board of Directors or advisory committees; Novo Nordisk: Educational Support and Travel Grants, Educational Support and Travel Grants Other; OctaPharma: Educational Support and Travel Grants Other, Membership on an entity9s Board of Directors or advisory committees; Pfizer: Educational Support and Travel Grants Other, Membership on an entity9s Board of Directors or advisory committees. Barnes:Baxter: Membership on an entity9s Board of Directors or advisory committees; Bayer: Educational support and travel grants, Educational support and travel grants Other, Membership on an entity9s Board of Directors or advisory committees; Biogen Idec: Honoraria, Membership on an entity9s Board of Directors or advisory committees; Novo Nordisk: Educational support and travel grants, Educational support and travel grants Other, Honoraria, Membership on an entity9s Board of Directors or advisory committees, Research Funding; Pfizer: Educational support and travel grants Other, Honoraria, Speakers Bureau. Neelakantan:Biogen Idec: Employment, Equity Ownership. Gambino:Biogen Idec: Employment, Equity Ownership. Cristiano:Biogen Idec: Employment, Equity Ownership. Barnowski:Biogen Idec: Employment, Equity Ownership. Pierce:Biogen Idec: Employment, Equity Ownership. Allen:Biogen Idec: Employment, Equity Ownership.