Agradecimentos: This study was funded by Biogen Idec, Cambridge, MA, USA. J. Powell, A. Shapiro, M. Ragni, C. Negrier, J. Windyga, M. Ozelo, J. Pasi, and R. Baker contributed to the collection and interpretation of data and drafting and revising of the manuscript. G.F. Pierce, B. Robinson, and S. Li contributed to the design and conceptualization of this research, design of data analyses, interpretation of data, and drafting and revising of the manuscript. J. Potts contributed to the design of data analyses, performed the statistical analyses, and contributed to the interpretation of the data and editing of the manuscript. B. Mei contributed to the design of data analyses, collection and interpretation of data, and drafting and editing of the manuscript. The authors retained full editorial control over the content of the manuscript. We would like to thank Aoife Brennan, MB, BCh, BAO, and Haiyan Jiang, PhD, of Biogen Idec for reviewing and providing input on the manuscript. Editorial support for the writing of this manuscript was provided by Katie Gersh, PhD, of MedErgy, and MaryEllen Carlile Klusacek, PhD, of Biogen Idec, and was funded by Biogen Idec Ver menos

Abstract: In the phase 3 B-LONG [Recombinant Factor IX Fc Fusion Protein (rFIXFc) in Subjects with Haemophilia B] study, rFIXFc dosed every 1–2 weeks was safe and efficacious in previously treated subjects with haemophilia B. To date, there are no evaluations of transitioning from conventional to long-acting factor IX (FIX) prophylaxis. This post-hoc analysis of B-LONG subjects compared prophylaxis with other FIX products and rFIXFc. Pre- and on-study data were analysed to assess dosing regimen, weekly FIX consumption and annualized bleeding rates (ABRs). Population pharmacokinetics models were used to generate FIX activity profiles with rFIXFc and recombinant FIX prophylaxis. Thirty-nine subjects, previously treated prophylactically, were evaluated. Prior to study, most subjects (69·2%) received twice-weekly FIX infusions; on study, subjects infused rFIXFc once every 1–2 weeks with c. 30–50% reductions in weekly consumption. On-study estimated mean ABRs were lower than pre-study estimated mean ABRs. Models predicted that rFIXFc administered 50 iu/kg weekly and 100 iu/kg every 10 d would maintain steady-state FIX trough levels =1 iu/dl in 95·4% and 89·2% of subjects, respectively. These results indicate that patients receiving rFIXFc prophylaxis can markedly reduce infusion frequency and FIX consumption, have a greater likelihood of maintaining FIX activity >1 iu/dl and experience fewer bleeding episodes compared with prior FIX prophylaxis Ver menos