Dosing regimens before and during long-term treatment with recombinant factor VIII FC fusion protein (rFVIIIFc) in adults and adolescents with severe haemophilia a: An updated analysis of the aspire study

Abstract

Introduction: Here we report changes in dosing regimen from that used prior to the pivotal study (ALONG) in adults and adolescents to that used at the third interim data cut of the ongoing extension study of rFVIIIFc (ASPIRE). Methods: Eligible subjects aged ≥12 y with severe haemophilia A (<1 IU dL-1 [1%] endogenous FVIII activity) who completed the Phase 3 A-LONG study could enroll in 1 of 4 treatment groups in ASPIRE: individualised prophylaxis (IP; 25-65 IU kg-1 every 3-5 days, or 20-65 IU kg-1 on Day 1 and 40- 65 IU kg-1 on Day 4 if twice-weekly); weekly prophylaxis (WP; 65 IU kg-1 every 7 days); modified prophylaxis (MP; for those needing additional dose optimization), or episodic treatment. Subjects could change treatment groups at any time in ASPIRE. Subjects with available prestudy (pre-A-LONG) FVIII and on-study rFVIIIFc dosing data were evaluated for changes in injection frequency and total weekly prophylactic factor consumption (IU kg-1 week-1) at the third ASPIRE interim data cut (11 January 2016) in this post hoc analysis. Results: Of 150 subjects from A-LONG who enrolled in ASPIRE, 56 completed, 16 discontinued, and 78 remained in ASPIRE as of the third interim data cut. From the first rFVIIIFc injection in A-LONG to the third interim data cut, the median cumulative duration of treatment was 4.1 (range, 0.7-4.6) y. Among subjects treated with FVIII prophylactically prestudy (n = 79), 76 (96.2%) lengthened, 2 (2.5%) shortened, and 1 (1.3%) had no change to their dosing interval with rFVIIIFc (vs prestudy intervals) as of the third interim data cut. Furthermore, 38 (48.1%) subjects reduced, 38 (48.1%) increased, and 3 (3.8%) had no change in their total weekly prophylactic factor consumption with rFVIIIFc (vs prestudy FVIII). The median (IQR) change in the total weekly prophylactic factor consumption from prestudy to the third interim data cut was 0.0 (-17.0-26.7) IU kg-1 week-1. Median (IQR) annualised bleeding rates were low with rFVIIIFc prophylaxis (IP, 0.8 [0.0-2.7]; WP, 2.2 [0.4-5.1]; MP, 4.1 [1.2-10.4]). Discussion/Conclusion: Over an extended time period, adults and adolescents with severe haemophilia A maintained lengthened prophylactic dosing intervals, with similar weekly factor consumption with rFVIIIFc compared to prestudy FVIII regimens.L6145110282017-02-27 <br />