Objective:
Recombinant factor VIII Fc fusion protein (rFVIIIFc) is an extended half-life FVIII therapy approved for treatment of adults and children with hemophilia A. A-LONG parent (NCT01181128) and ASPIRE extension (NCT01454739) Phase 3 studies evaluated safety and efficacy of rFVIIIFc for prevention and treatment of bleeding episodes for previously treated subjects with severe hemophilia A. A subgroup analysis was performed using A-LONG and ASPIRE interim data cut 3 and including subjects ≥50 years of age.
Methods:
Subjects were assigned to one of the following treatment regimens: individualized prophylaxis (IP; 25–65 IU/kg rFVIIIFc every 3–5 days), weekly prophylaxis (WP; 65 IU/kg every 7 days), modified prophylaxis (MP; tailored dosing if IP and WP were suboptimal), and episodic treatment (ET; on-demand dosage dependent on type and severity of bleeding episode). Subjects could change treatment groups at any time in ASPIRE and may appear in more than one treatment regimen. For this subgroup analysis outcomes included inhibitor development, the annualized bleeding rate (ABR), ABRs for subjects with target joints and target joint resolution, hemophilia quality of life questionnaire for adults (Hem-A-QoL), modified hemophilia joint health score (mHJHS), and cumulative exposure.
Summary:
Twenty-one subjects ≥50 years of age (median [range] age, 57 [50–65] years) in A-LONG and/or ASPIRE received rFVIIIFc (IP, n = 14; WP, n = 7; MP, n = 3; ET, n = 3). Baseline median (interquartile range [IQR]) ABR was 13 (6–22) for subjects who received pre-study prophylaxis and 27 (19–43) for subjects who received pre-study ET. No subjects developed inhibitors. Median (IQR) ABRs on treatment (with n ≥5) were 1.77 (0.35–5.26; IP) and 2.01 (0.25–4.76; WP). On-treatment ABRs (median [IQR]) for subjects with target joints (with n ≥5) were 1.39 (0.00–5.26; IP) and 2.01 (0.25–4.76; WP). All 49 evaluable target joints were resolved during prophylactic treatment. Mean (standard deviation) change from baseline in total Hem-A-QoL score and mHJHS was –1.9 (10.9) and –9.2 (11.43), respectively, for subjects who were always on prophylactic rFVIIIFc treatment. Subjects had a median (IQR) of 4.05 (3.04–4.26) years of treatment with rFVIIIFc and 293 (227–364) cumulative rFVIIIFc exposure days. There was no increase in weekly factor consumption.
Conclusions:
For previously treated subjects ≥50 years of age with severe hemophilia A, rFVIIIFc prophylaxis for approximately 4 years resulted in low ABRs and improved/sustained joint health without inhibitor development and without increase in factor consumption, suggesting that rFVIIIFc prophylaxis in adults ≥50 years of age has overall clinical benefits irrespective of baseline status. These data were similar to the overall study population.