Continuous prophylaxis with recombinant factor IX Fc fusion protein and conventional recombinant factor IX products: comparisons of efficacy and weekly factor consumption

Iorio, Alfonso; Krishnan, Sangeeta; Myrén, Karl-Johan; Lethagen, Stefan; McCormick, Nora; Yermakov, Sander; Karner, Paul

doi:10.6084/m9.figshare.4258313.v2

ijme_a_1265973_sm9312.docx (256.87 kB)

Continuous prophylaxis with recombinant factor IX Fc fusion protein and conventional recombinant factor IX products: comparisons of efficacy and weekly factor consumption

Version 2 2017-02-01, 09:19

Version 1 2016-11-25, 15:08

journal contribution

posted on 2017-02-01, 09:19 authored by Alfonso Iorio, Sangeeta Krishnan, Karl-Johan Myrén, Stefan Lethagen, Nora McCormick, Sander Yermakov, Paul Karner

Background: Continuous prophylaxis for patients with hemophilia B requires frequent injections that are burdensome and that may lead to suboptimal adherence and outcomes. Hence, therapies requiring less-frequent injections are needed. In the absence of head-to-head comparisons, this study compared the first extended-half-life-recombinant factor IX (rFIX) product—recombinant factor IX Fc fusion protein (rFIXFc)—with conventional rFIX products based on annualized bleed rates (ABRs) and factor consumption reported in studies of continuous prophylaxis.

Methods: This study compared ABRs and weekly factor consumption rates in clinical studies of continuous prophylaxis treatment with rFIXFc and conventional rFIX products (identified by systematic literature review) in previously-treated adolescents and adults with moderate-to-severe hemophilia B. Meta-analysis was used to pool ABRs reported for conventional rFIX products for comparison. Comparisons of weekly factor consumption were based on the mean, reported or estimated from the mean dose per injection.

Results: Five conventional rFIX studies (injections 1 to >3 times/week) met the criteria for comparison with once-weekly rFIXFc reported by the B-LONG study. The pooled mean ABR for conventional rFIX was slightly higher than but comparable to rFIXFc (difference=0.71; p = 0.210). Weekly factor consumption was significantly lower with rFIXFc than in conventional rFIX studies (difference in means = 42.8–74.5 IU/kg/week [93–161%], p < 0.001).

Conclusion: Comparisons of clinical study results suggest weekly injections with rFIXFc result in similar bleeding rates and significantly lower weekly factor consumption compared with more-frequently-injected conventional rFIX products. The real-world effectiveness of rFIXFc may be higher based on results from a model of the impact of simulated differences in adherence.