Long-term efficacy of recombinant factor VIII FC Fusion Protein (rFVIIIFC) prophylaxis in paediatric, adolescent, and adult subjects with target joints and severe haemophilia A

Abstract

Introduction: Here we report longitudinal data from subjects with target joints at entry into A-LONG and Kids A-LONG throughout the ongoing rFVIIIFc extension study, ASPIRE (NCT01454739). Methods: There are 4 treatment groups in ASPIRE for subjects ≥12 year: individualised prophylaxis (IP), weekly prophylaxis (WP), modified prophylaxis (MP; for subjects not achieving optimal dosing with IP or WP), or episodic treatment. Subjects <12 year can participate in IP or MP. Subjects with ≥1 target joint (major joint with ≥3 bleeding episodes in a 6-month period) at entry into the parent study with available prestudy (pre-parent study) and on-study data were evaluated. Outcomes were analysed over the cumulative duration of the parent study through the ASPIRE interim data cut (6 Jan 2014). Results: 113 A-LONG subjects had target joints at baseline (BL); 111 had prestudy and on-study data. These 111 subjects had 287 target joints at BL (elbow [n = 100; 34.8%], ankle [n = 92; 32.1%], knee [n = 63; 22.0%], shoulder [n = 17; 5.9%], wrist [n = 9; 3.1%], hip [n = 6; 2.1%]). 13 Kids A-LONG subjects had 15 target joints at BL (ankle [n = 10; 66.7%], elbow [n = 4; 26.7%], knee [n = 1; 6.7%]). In subjects with target joints at BL, median (IQR) onstudy overall annualised bleeding rates (ABRs) with rFVIIIFc prophylaxis were lower than bleeding rates with prestudy prophylaxis for adults/adolescents (onstudy: IP, 1.9 [0.4-3.7]; WP, 2.0 [1.0-4.8]; MP, 4.4 [1.3-9.6] vs. prestudy: 12.5 [6-24]) and children (onstudy: IP, 1.9 [0-5.7] vs. prestudy: 6.5 [2-8]). Onstudy spontaneous target joint median (IQR) ABRs were low for adults/adolescents (IP, 0 [0-0.9]; WP, 0 [0-1.0]; MP, 0.3 [0-3.7]) and children (IP, 0 [0-2.0]). 47.6% of IP, 42.3% of WP, and 41.7% of MP subjects had no target joint bleeding episodes during A-LONG/ASPIRE; 53.8% of Kids A-LONG subjects in the IP group had no target joint bleeding episodes on-study. 99% (91/92) A-LONG prophylaxis subjects with target joints at BL and 12 month follow-up had ≥1 target joint resolved. Prophylactic dosing and dosing intervals for subjects with target joints at BL were similar to the overall study populations. Discussion/Conclusion: Efficacy data from the phase 3 and extension trials show low target joint ABRs with extended dosing intervals in subjects on longterm rFVIIIFc prophylaxis.L6224702392018-06-11 <br />