Real-world usage and effectiveness of recombinant factor IX Fc in haemophilia B from the B-SURE study in France

Abstract

Background: More real-world data are needed to complement existing phase III studies on the efficacy and safety of recombinant factor IX Fc fusion protein (rFIXFc) in people with haemophilia B.

Objectives: We report final data from the B-SURE study, evaluating the real-world usage and effectiveness of rFIXFc in France.

Methods: Previously treated patients (all ages/severities) received on-demand or prophylactic rFIXFc during B-SURE. Annualised bleeding rate (ABR), injection frequency (IF) and factor consumption (FC) were prospectively evaluated for patients on rFIXFc prophylaxis (primary endpoints). Six months of retrospective factor IX (FIX) data were collected for comparison; patients with ⩾3 months of treatment pre- and post-switch to rFIXFc were analysed.

Design: B-SURE was a 24-month, prospective, non-interventional, real-world study across haemophilia treatment centres in France.

Results: Ninety-one male patients enrolled across 21 centres (34% <18 years, 89% severe haemophilia B). Eighty-four patients received prophylaxis at rFIXFc initiation; mean prospective observation period was 21.5 months. Sixty-eight of 84 patients had prior FIX prophylaxis; on rFIXFc prophylaxis, these patients achieved low median ABR (1.2), IF (47.45 injections/year) and mean FC (2844 IU/kg/year). Compared with previous FIX, mean ABR was reduced by 40% (n = 63); mean IF and FC were reduced by 38.20 injections/year and 1008 IU/kg/year (n = 57). In patients with prior FIX on-demand (n = 15), mean ABR reduced by 84% on rFIXFc prophylaxis (n = 14), mean IF reduced by 2.13 injections/year and mean FC increased by 381.8 IU/kg/year (n = 15). Most physicians and patients were satisfied/highly satisfied with rFIXFc prophylaxis. rFIXFc was well tolerated with no new safety concerns.

Conclusion: Findings support the safety and effectiveness of rFIXFc, with reduced IF and FC while maintaining/improving bleed protection. Trial registration: NCT03655340.

Keywords: factor IX; haemophilia B; prophylaxis; recombinant fusion proteins.

Graphical Abstract

Figure 1.

B-SURE study design. FIX, factor IX; rFIXFc, recombinant factor IX Fc fusion protein.

Figure 2.

Treatment regimens pre- and post-switch to rFIXFc. ^aFinal rFIXFc regimen refers to the last documented regimen. ^bOne patient had multiple switches between prophylaxis and on-demand treatment regimens since rFIXFc prophylaxis initiation; final regimen was on-demand treatment. FIX, factor IX; rFIXFc, recombinant factor IX Fc fusion protein.

Figure 3.

ABR of patients with available data both pre- and post-switch to rFIXFc prophylaxis from (a) FIX prophylaxis (n = 63) or (b) FIX on-demand treatment (n = 14). Figure shows means (triangles), IQR (box boundaries) and ranges (error bars); orange line indicates equal median/quartile. The period prior to rFIXFc initiation refers to the 6 months prior to the first rFIXFc injection; the period since rFIXFc initiation refers to the period from the first rFIXFc injection to the end of the prospective period. Means were estimated using a negative binomial model with the total number of treated bleeding episodes during the efficacy period as the response variable and log-transformed period duration (in years) as an offset variable. RRs were estimated using a repeated negative binomial model with treatment period (prior versus post rFIXFc initiation) as a covariate. ^an = 63/65 patients with available data both pre- and post-switch to rFIXFc prophylaxis were included. ^bn = 14/18 patients with available data both pre- and post-switch to rFIXFc prophylaxis were included. ABR, annualised bleeding rate; AJBR, annualised joint bleeding rate; FIX, factor IX; IQR, interquartile range; rFIXFc, recombinant factor IX Fc fusion protein; RR, rate ratio.