Switching to recombinant factor IX Fc fusion protein prophylaxis results in fewer infusions, decreased factor IX consumption and lower bleeding rates

Abstract

SummaryIn 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 (69Á2%) 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 95Á4% and 89Á2% 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.

Long‐acting recombinant factor IX Fc fusion protein (rFIXFc) for perioperative management of subjects with haemophilia B in the phase 3 B‐LONG study

“…Results from the non‐surgical arms of the multicentre phase 3 B‐LONG [Recombinant Factor IX Fc Fusion Protein (rFIXFc) in Subjects With Haemophilia B] study demonstrated a prolonged half‐life and lower consumption of recombinant FIX Fc fusion protein (rFIXFc), relative to rFIX, and the safety and efficacy of rFIXFc for treatment of bleeding and routine prophylaxis with dosing intervals of 1–2 weeks, which is longer than intervals seen with historical trials of rFIX (Powell et al , ; Powell et al , ). Here, we describe the surgical experience with rFIXFc in subjects with haemophilia B enrolled in B‐LONG.…”

In silico evaluation of limited blood sampling strategies for individualized recombinant factor IX prophylaxis in hemophilia B patients

“…In this study, individual PK profiles for rFIX were created for 5000 virtual patients by Monte Carlo simulation [12]. Monte Carlo simulation with the population pharmacokinetics of clotting factors is increasingly being used in hemophilia [13][14][15][16][17][18][19], although not extensively. Therefore, the principles of this technique are described below.…”

Changing Paradigm of Hemophilia Management: Extended Half-Life Factor Concentrates and Gene Therapy

“…Posthoc analysis of the study demonstrated that prophylaxis with rFIXFc markedly reduced infusion frequency and FIX consumption; additionally, rFIXFc when administered weekly or every 10 days would maintain steady-state FIX activity greater than 1% in 95% and 89% of the patients, respectively. 52 Hemostatic response in 14 patients undergoing surgery was rated to be excellent (n ¼ 13) or good (n ¼ 1). 53 Interim analysis of the ongoing pediatric trial [NCT 014409046] reported the use of rFIXFc in 24 previously treated pediatric patients (age < 12 years) with HB (FIX activity 2 IU/dL).…”