R Liesner1, C Akanezi2, M Norton2, J Payne3. 1. Haemophilia Comprehensive Care Centre, Great Ormond Street Hospital, London, UK. 2. Bio Products Laboratory Ltd, Elstree, UK. 3. Department of Paediatric Haematology, Sheffield Children's NHS Foundation Trust, Sheffield, UK.
Abstract
BACKGROUND: Hereditary factor X (FX) deficiency (FXD) affects 1:500 000-1:1 000 000 people worldwide. A novel, high-purity plasma-derived FX concentrate (pdFX) is available in the United States and European Union as replacement therapy for FXD, but data are scarce on pdFX use in children <12 years. AIM: This prospective, open-label phase 3 study assessed the safety, efficacy and pharmacokinetics of pdFX in children <12 years with moderate/severe FXD. METHODS: Subjects aged <12 years with basal plasma FX activity (FX:C) <5 IU/dL received pdFX as prophylactic and on-demand treatment, with doses adjusted to maintain FX:C > 5 IU/dL. After ≥26 weeks and ≥50 exposure days, investigators rated pdFX efficacy for preventing/decreasing bleeds. Secondary endpoints included number and severity of bleeds, trough FX:C and incremental recovery. Safety parameters were adverse events (AEs), inhibitor development and changes in laboratory parameters. RESULTS: The study enrolled 9 subjects (0-5 years, n = 4; 6-11 years, n = 5) with severe (n = 8) or moderate (n = 1) FXD. At end of study, investigators rated pdFX efficacy excellent for all subjects. Ten bleeds occurred (n = 3 subjects; 6 major, 3 minor, 1 unassessed for severity). Trough FX:C levels remained >5 IU/dL for all subjects after the last dose adjustment study visit. Mean incremental recovery was significantly lower for younger vs older subjects (1.53 vs 1.91 IU/dL per IU/kg; P = .001). All AEs were unrelated to treatment; no inhibitor development or clinically significant changes in laboratory parameters were observed. CONCLUSIONS: These results demonstrate the efficacy and safety of pdFX for treating children <12 years with moderate/severe hereditary FXD.
BACKGROUND: Hereditary factor X (FX) deficiency (FXD) affects 1:500 000-1:1 000 000 people worldwide. A novel, high-purity plasma-derived FX concentrate (pdFX) is available in the United States and European Union as replacement therapy for FXD, but data are scarce on pdFX use in children <12 years. AIM: This prospective, open-label phase 3 study assessed the safety, efficacy and pharmacokinetics of pdFX in children <12 years with moderate/severe FXD. METHODS: Subjects aged <12 years with basal plasma FX activity (FX:C) <5 IU/dL received pdFX as prophylactic and on-demand treatment, with doses adjusted to maintain FX:C > 5 IU/dL. After ≥26 weeks and ≥50 exposure days, investigators rated pdFX efficacy for preventing/decreasing bleeds. Secondary endpoints included number and severity of bleeds, trough FX:C and incremental recovery. Safety parameters were adverse events (AEs), inhibitor development and changes in laboratory parameters. RESULTS: The study enrolled 9 subjects (0-5 years, n = 4; 6-11 years, n = 5) with severe (n = 8) or moderate (n = 1) FXD. At end of study, investigators rated pdFX efficacy excellent for all subjects. Ten bleeds occurred (n = 3 subjects; 6 major, 3 minor, 1 unassessed for severity). Trough FX:C levels remained >5 IU/dL for all subjects after the last dose adjustment study visit. Mean incremental recovery was significantly lower for younger vs older subjects (1.53 vs 1.91 IU/dL per IU/kg; P = .001). All AEs were unrelated to treatment; no inhibitor development or clinically significant changes in laboratory parameters were observed. CONCLUSIONS: These results demonstrate the efficacy and safety of pdFX for treating children <12 years with moderate/severe hereditary FXD.
Authors: Jeanette Payne; Glaivy Batsuli; Andrew D Leavitt; Mary Mathias; Catherine E McGuinn Journal: Haemophilia Date: 2022-05-02 Impact factor: 4.263