Program: Oral and Poster Abstracts
Session: 322. Disorders of Coagulation or Fibrinolysis: Poster III
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.
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.
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).
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.
Disclosures: Shapiro: Kedrion Biopharma: Research Funding; Bayer HealthCare: Research Funding; Daiichi Sankyo: Research Funding; Biogen: Consultancy, Research Funding, Speakers Bureau; Octapharma: Research Funding; Kedrion Biopharma: Consultancy; ProMetic Life Sciences: Consultancy, Research Funding; Baxalta: Consultancy, Research Funding; CSL Behring: Research Funding; OPKO: Research Funding; PTC Therapeutics: Research Funding; Selexys: Research Funding; Novo Nordisk: Consultancy. Ozelo: Novo Nordisk: Consultancy, Research Funding, Speakers Bureau; Grifols: Speakers Bureau; Shire: Consultancy, Research Funding, Speakers Bureau; Pfizer: Consultancy, Research Funding, Speakers Bureau; Roche: Consultancy, Speakers Bureau; CSL Behing: Consultancy; Biogen: Consultancy, Research Funding, Speakers Bureau. Pasi: Alnylam Pharmaceuticals; BioMarin Pharmaceutical Inc.; SOBI: Membership on an entity's Board of Directors or advisory committees; Roche, NovoNordisk, Pfizer: Other: paid instructor; BioMarin Pharmaceutical Inc.; Octapharma, Alnylam Pharmaceuticals, Bioverativ: Research Funding; Pfizer, SOBI, Octapharma, Shire, Bayer, Alnylam, Biomarin, Biotest: Honoraria; Bayer HealthCare; Biotest; Novo Nordisk; Pfizer Inc.; Roche: Speakers Bureau; Alnylam Pharmaceuticals, Inc; Biogen Idec Inc.; BioMarin Pharmaceutical Inc.; Octapharmal; Roche; Shire; SOBI: Consultancy. Feng: Bioverativ: Employment, Equity Ownership. Winding: Sobi, BR, Bent: Employment. Barnowski: Bioverativ: Employment, Equity Ownership. Kulkarni: Novo, Shire, Bioverative, Kedrion, BPL, Pfizer: Membership on an entity's Board of Directors or advisory committees, Other: participated in clinical trials; Bayer: Other: participated in clinical trials.
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