Long‐term safety and efficacy of recombinant factor VIII Fc fusion protein (rFVIIIFc) in subjects with haemophilia A

Abstract

Introduction The safety, efficacy and prolonged half‐life of recombinant factor VIII Fc fusion protein (rFVIIIFc) in previously treated patients with severe haemophilia A was demonstrated in the phase 3 A‐LONG and Kids A‐LONG studies. Here, we report interim safety and efficacy data from the rFVIIIFc extension study, ASPIRE (ClinicalTrials.gov #NCT01454739). Methods Eligible subjects could enrol in ASPIRE upon completing A‐LONG or Kids A‐LONG. There were four treatment groups: individualized prophylaxis; weekly prophylaxis; modified prophylaxis (for subjects in whom optimal treatment could not be achieved with individualized or weekly prophylaxis); and episodic treatment. The primary endpoint was development of inhibitors. Results A total of 150 A‐LONG subjects and 61 Kids A‐LONG subjects enrolled in ASPIRE. As of the interim data cut (6 January 2014), the median time on study was 80.9 (A‐LONG) and 23.9 (Kids A‐LONG) weeks. The majority of subjects (A‐LONG, 92.0%; Kids A‐LONG, 57.4%) had ≥100 cumulative rFVIIIFc exposure days. No inhibitors were observed. Adverse events were generally consistent with those expected in the general haemophilia A population. Median annualized bleeding rates (ABRs) were low with individualized [A‐LONG: 0.66; Kids A‐LONG: 0.00 (<6 years old), 1.54 (6 to <12 years old)], weekly (A‐LONG: 2.03) and modified (A‐LONG: 1.97) prophylaxis. There was no change in prophylactic infusion frequency or total weekly prophylactic dose in the majority of subjects from A‐LONG and Kids A‐LONG. Conclusion Interim data from ASPIRE confirm the long‐term safety of rFVIIIFc and the maintenance of a low ABR with extended‐interval prophylactic dosing in patients with severe haemophilia A.

Outcome of Clinical Trials with New Extended Half-Life FVIII/IX Concentrates

“…The long-term safety and efficacy of rFVIIIFc was further evaluated in the frame of an extension trial (NCT01454739; ASPIRE) that included 150 and 61 subjects coming from A-LONG and Kids A-LONG studies, respectively, and who have received more than 100 cumulative exposure days (EDs) to rFVIIIFc [16]. Efficacy and safety results confirmed those obtained in the pivotal trials with a better ABR in patients treated according to an individualized regimen.…”

“…Efficacy and safety results confirmed those obtained in the pivotal trials with a better ABR in patients treated according to an individualized regimen. The vast majority of patients (i.e., 64% of adults and 79% of children) did not change infusion frequency or total weekly prophylactic dose, while 20% and 12% of adults and children reduced their total weekly dose during the extension phase [16]. …”

Extended Half-Life Factor VIII and Factor IX Preparations

“…Interim data of an rFVIIIFc extension study confirm both longterm safety and maintenance of low ABRs with extended interval prophylactic dosing [29].…”

Comparative evaluation of the safety and efficacy of recombinant FVIII in severe hemophilia A patients

“…Long-term use of this recombinant FVIII maintained the low average bleeding rate and increased intervals of prophylactic injections [21]. …”

“…Efficacy of pegylated full-length recombinant FVIII for the prophylactic and on-demand management of patients with severe hemophilia A was assessed by Konkle and creased intervals of prophylactic injections [21]. …”