Safety and efficacy of investigator‐prescribed BeneFIX^® prophylaxis in children less than 6 years of age with severe haemophilia B

Abstract

Prophylaxis is increasingly prescribed in treatment of haemophilia and its benefit is believed to be most significant for the youngest patients as haemophilic arthropathy may be prevented if prophylaxis is initiated prior to recurrent haemarthroses. While clinical prophylaxis data are readily available for haemophilia A, analogous data for haemophilia B are relatively limited. A prospective clinical study of recombinant factor IX (BeneFIX; rFIX), designed to allow investigator prescribed prophylaxis according to customary practices, was conducted in children <6 years old with severe haemophilia B. Nearly all children were prescribed prophylaxis (22/25; 88%) for all or part of their study participation. Favourable efficacy and safety profiles were reported. Routine prophylaxis with 1 or 2 rFIX infusions per week over an average of greater than 6 months of therapy resulted in near complete prevention of spontaneous breakthrough haemorrhages (<1 per year), with most children (77%) having none, including seven patients (32%) who had no bleeding episodes at all. Haemorrhages in joints were less common than those outside joints (27% vs. 73% of haemorrhages). In a patient population that included children with multiple prior haemarthroses, 68% of children had no joint bleeding. Breakthrough haemorrhages resolved with 1 or 2 infusions in 89% of episodes. The absence of changes in prophylaxis infusion schedules suggests that 1 or 2 rFIX infusion(s) per week were well-tolerated by these young patients, including those with (41%) and without (59%) central venous access devices. Safety was established by the low incidence of treatment-related adverse events.

Recombinant long-acting glycoPEGylated factor IX in hemophilia B: a multinational randomized phase 3 trial

“…18,20,21,23 The predefined criteria for effective prophylaxis (estimated mean ABR significantly below 4.8) were met with the 40 IU/kg dose, but not the 10 IU/kg dose, despite a clinical effect with both doses. In the 40 IU/kg group, 45% of the patients did not bleed at all; this proportion was 17% in the 10 IU/kg group.…”

Evaluation of Nonacog Beta Pegol Long-term Safety in the Immune-deficient Rowett Nude Rat (Crl:NIH-Foxn1rnu)

“…For toxicity testing, the nude rat model has a disadvantage in lacking a large amount of background data, meaning that differentiating between pathological findings being related to treatment or to the model could be challenging. However, in this case, the risk of unexplainable toxicity was considered minimal, based on the long-term clinical knowledge of risks related to rFIX (Berntorp et al 2012;Monahan et al 2010;Roth et al 2001). Thus, a case-by-case approach is suggested when considering the nude rat as a chronic toxicity model.…”

Prolonged half-life and preserved enzymatic properties of factor IX selectively PEGylated on native N-glycans in the activation peptide

“…When adhered to, prophylaxis in patients without severe joint disorder is efficacious with a frequency of only 0-2 breakthrough bleeds per year in the majority of patients. 8,10 However, the need for multiple weekly infusions present challenges in terms of repeated venous access which may affect adherence to treatment and necessitate placement of indwelling catheters with the inherent risk of infection. 11 Various approaches have been pursued to extend the half-life of coagulation factors including genetic fusions to albumin and the Fc fragment of IgG as well as chemical modification by hydrophilic polymers such as polyethylene glycol (PEG).…”