Safe switching from a pdFIX (Immunine^®) to a rFIX (Bax326)

Abstract

The ability to switch between coagulation factors safely is of common interest to haemophilia patients and treating physicians. This is the first formal prospective comparative evaluation of safety, efficacy and incremental recovery of a plasma-derived FIX (pdFIX) and a recombinant FIX (rFIX) in the same haemophilia B patients following a switch from pdFIX Immunine® to a recently developed rFIX Bax326 product. Patients (aged <65 years) who completed a pretreatment study which prospectively documented the exposure to Immunine® and monitored FIX inhibitors while receiving prophylactic treatment were transitioned into pivotal (patients aged 12-65 years) and paediatric (patients aged <12 years) clinical studies investigating prophylaxis and treatment of bleeding episodes with Bax326. None of the 44 patients developed inhibitory or specific binding anti-FIX antibodies during the course of the studies. A total of 38 unrelated adverse events (AEs) were occurred in 20/44 (45.5%) subjects during the Immunine® study. Following a switch to Bax326, 51 AEs were reported in 25/44 (56.8%) subjects. The incidence of AEs related to Bax326 treatment (two episodes of dysgeusia in one patient) was low (2.3%); there were no serious adverse reactions. The comparison between Immunine® and Bax326 demonstrated analogous haemostatic characteristics and annualized bleeding rates. Overall, there is direct evidence indicating a safe and clinically effective transition from a pdFIX (Immunine®) to a newly developed rFIX (Bax326(1) ) for prophylaxis and treatment of bleeding in previously treated patients of all age cohorts with severe or moderately severe haemophilia B.

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

“…However, subject‐reported pre‐study weekly consumption and bleeding rates were generally similar to those seen in clinical trials of rFIX (Table ) (Roth et al , ; Lambert et al , ; Valentino et al , ; Windyga et al , ,b) and pdFIX (Nilsson et al , ; Lindvall et al , ); the similarity in bleeding rates suggests that pre‐study prophylaxis compliance may have been similar to that observed in clinical trials of FIX therapies. Parallels can also be drawn to a recent study in which ABRs were lowered by switching from pdFIX to rFIX (Solano Trujillo et al , ); although data on factor consumption were not included in this study, dosing regimens were similar to the pre‐study rFIX regimens included for comparison in Table , further supporting the regimens modelled in our analysis as ‘typical’ of clinical practice. Finally, study participants who had received prophylactic pdFIX pre‐study were assigned disproportionately to weekly prophylaxis on‐study, probably related to regional and individual patient treatment preferences.…”

Systematic review and analysis of efficacy of recombinant factor IX products for prophylactic treatment of hemophilia B in comparison with rIX-FP

“…These studies included EHL rFIX products, with one study of rIX-FP (IDELVION 8 ), one study of rFIXFc (Alprolix 9 ), and two studies of N9-GP (Refixia 10,14 ). Standard-acting rFIX products were also included, with two studies of rFIX (BeneFIX 13,15 ), two studies of BAX 326 (Rixubis 16,17 ), and one study of IB1001 (Ixinity 18 ). Following further evaluation, one of the articles reporting on BAX 326 was excluded, as this publication included all patients who had completed a pre-treatment study, followed by pivotal trials in adults and pediatrics 17 .…”

BAX326 (RIXUBIS): a novel recombinant factor IX for the control and prevention of bleeding episodes in adults and children with hemophilia B

“…Immunine exposure and FIX inhibitor formation were monitored during prophylactic treatment over approximately 20-50 exposure days. The study also ensured that patients were adequately pretreated and met the inclusion criterion for the pivotal or pediatric studies (150 exposure days for patients aged ⩾6 years and 50 for patients aged <6 years) [Solano Trujillo et al 2014]. …”

“…A total of 32 patients were aged ⩾12 years (median 29.5 years) and subsequently entered the pivotal BAX326 study; 12 patients were aged <12 years (median 7.5 years) and were later enrolled in the pediatric study (Table 2) [Solano Trujillo et al 2014].…”