Bleed Protection with up to 14-Day Dosing of Long-Acting Recombinant Factor IX Product in Selected Children with Hemophilia B

In pharmacokinetic studies, a recombinant fusion protein genetically linking human coagulation factor IX with human albumin (rIX-FP) (IDELVION, CSL Behring) has been shown to have an approximately five-fold longer half-life compared with standard recombinant factor IX products. Following a pivotal Phase III study in which children with moderate to severe hemophilia B received weekly prophylaxis, a Phase 3b prospective, multicenter extension study assigned 24 participants to a sevenday (25-50 IU/kg), 10-day or 14-day (50-75 IU/kg) regimen for approximately 30 months. Investigator and subject preference dictated the dosing frequency for the first six months of the study. At six-month intervals thereafter, the investigator could change the regimen based on an assessment of efficacy, safety, treatment compliance and/or preference. Among various endpoints evaluated across the three dosing regimens were spontaneous annualized bleeding rate (AsBR) and monthly consumption of rIX-FP. Compared with their initial six-month starting regimen, by the end of the study, dosing intervals were the same, extended and shortened in 16, four and four subjects, respectively. Seventeen, three and four subjects, respectively, ended the study on the seven-, 10- and 14-day prophylaxis regimens. The respective median AsBRs were 0.0, 0.0 and 1.1. Subjects on a 14-day regimen maintained a mean steady-state trough factor IX level of >7.2 IU/dL.

Mean overall monthly consumption of rIX-FP, including both for prophylaxis and control of bleeding events, was 231.2, 224.2 and 185.4 IU/kg for the seven-, 10- and 14-day dosing regimens, respectively, with 4.6, 3.4 and 2.6 mean monthly infusions.

Noting that “reduced infusion frequency provides dosing flexibility,” the investigators concluded extended dosing intervals of 10 days or 14 days are feasible with rIX-FP in selected pediatric patients who are well controlled on a seven-day regimen, while still maintaining adequate efficacy.