Clinical Outcomes of 14-Day Prophylaxis with rFIXFc: Longitudinal Analysis of the B-LONG and B-YOND Study

Introduction

Despite the advent of extended half-life factor IX (FIX) products with the potential for 14 days or longer prophylactic dosing in patients with severe hemophilia B, long-term data on the use of ≥14-day dosing are lacking for prolonged periods of observation. A post hoc analysis of the B-LONG Phase 3 trial showed that ~50% of subjects in the individualized interval prophylaxis treatment arm (Arm 2, n=29) used extended dosing intervals (≥14 days) and had low annualized bleed rates (ABRs) that were similar to ABRs in subjects on other dosing intervals in Arm 2.¹

The purpose of this analysis was to evaluate whether sustained ≥14-day dosing with recombinant FIX Fc fusion protein (rFIXFc) can provide safe and effective protection from bleeding in selected patients with severe hemophilia B over time in a near real-world setting.

Methods

B-LONG (NCT01027364) enrolled 123 adults and adolescents ≥12 years of age into 1 of 4 treatment arms: weekly prophylaxis (50 IU/kg every 7 days, adjusted to maintain factor levels 1-3 IU/dL above baseline or higher if clinically indicated), individualized prophylaxis (100 IU/kg every 10 days, interval adjusted to maintain factor levels 1-3 IU/dL above baseline or higher if clinically indicated), episodic treatment (20-100 IU/kg as required), and perioperative management (40-100 IU/kg, as required).

B-YOND (NCT01425723) is a Phase 3 extension trial of the B-LONG study, evaluating the safety and efficacy of rFIXFc in adolescents and adults (≥12 years). Weekly prophylaxis in the B-YOND study was defined as ~20-100 IU/kg of rFIXFc every 7 days; individualized prophylaxis was defined as ~100 IU/kg rFIXFc every 8 to 16 days or twice monthly; modified prophylaxis was defined as personalized dosing for subjects in whom optimal prophylaxis could not be achieved using either weekly or individualized prophylaxis; and episodic dosing was based on type and severity of the bleeding episode.

This analysis focused on subjects who were exposed to ≥14-day dosing in the B-LONG/B-YOND study population. Endpoints include ABRs, spontaneous ABRs, and spontaneous joint ABRs. A subset of patients who ended on ≥14-day dosing were also analyzed.

Results

Twenty-two subjects were treated with a ≥14-day dosing interval at any time during B-LONG or B-YOND with a mean follow-up of 3.4 years. At the time of extending the dosing interval to ≥14 days, 18 subjects had been receiving individualized prophylaxis, 1 had received once-weekly prophylaxis, 2 had previously been on episodic treatment, and 1 had started B-LONG on ≥14-day prophylaxis. Before extending the dosing interval, 19 of the 22 subjects had been treated with rFIXFc on a median (interquartile range [IQR]) dosing interval of 10 (10, 12) days.

All subjects who were previously on 10-day dosing had 0 bleeds before switching to ≥14-day dosing.

Before rFIXFc treatment, 10 of 22 (45.5%) subjects received prophylaxis and 12 of 22 (54.5%) subjects were on episodic treatment. For 9 of the subjects on prestudy prophylaxis, median (IQR) ABR was 2 (1, 4). For 11 subjects on prestudy episodic treatment, median (IQR) ABR was 25 (22, 36). The median (IQR) duration of treatment on the ≥14-day regimen was 3.4 (1.8, 4.0) years.

ABRs for the 22 subjects treated with a dosing interval ≥14 days, as well as 16 subjects who ended treatment on a dosing interval ≥14 days can be found in the Table. For the 9 subjects on prestudy prophylaxis, there was no difference in ABR; median (IQR) ABR changed from 2 (1.0, 4.0) to 1.8 (0.9, 2.7). For the 11 subjects receiving prestudy episodic treatment, median (IQR) ABR changed from 25 (22, 36) to 1.4 (0.6, 5.8).

Conclusions

Subjects treated with ≥14-day dosing intervals were well controlled with a median spontaneous ABR of 0.7 over a median of 3.4 years.

Subjects achieving ≥14-day dosing intervals had been previously well controlled with a 10-day dosing regimen.

These data confirm that ≥14-day dosing is a safe and efficacious prophylaxis option for episodic therapy patients seeking the benefits of prophylactic treatment but with minimal treatment burden.

1. Shapiro AD, et al. THNSA 2016; Poster.

View largeDownload slide

View largeDownload slide

Close modal