Lissitchkov T, Hampton K, von Depka M, Hay C, Rangarajan S, Tuddenham E, Holstein K, Huth-Kühne A, Pabinger I, Knaub S, Bichler J, Oldenburg J
Specialised Hospital for Active Treatment "Joan Pavel", Sofia, Bulgaria.
Royal Hallamshire Hospital, Sheffield, UK.
Haemophilia. 2016 Mar;22(2):225-231. doi: 10.1111/hae.12793. Epub 2015 Aug 28.
Nuwiq [human cell line-derived recombinant factor VIII (human-cl rhFVIII)] is a new generation rFVIII protein, without chemical modification or fusion to any other protein, produced in a human cell line.
AIM/METHODS: This prospective, open-label, multinational phase III study assessed the efficacy and safety of human-cl rhFVIII in 32 adult previously treated patients (PTPs) with severe haemophilia A during standard prophylaxis for ≥6 months and ≥50 exposure days. Efficacy in treating bleeds and during surgical prophylaxis was also assessed.
Prophylactic efficacy, based on mean monthly bleeding rate, was rated as 'excellent' or 'good' in 97% of patients for all bleeds and in 100% of patients for spontaneous bleeds. Mean (SD) annualized bleeding rate was 2.28 (3.73) [median = 0.9] for all bleeds, 1.16 (2.57) [median = 0] for spontaneous bleeds and 1.00 (1.79) [median = 0] for traumatic bleeds. There were no bleeds in 50% of patients and there were no major, life-threatening bleeds. Efficacy was 'excellent' or 'good' in treating 28 (100%) of 28 bleeds. Overall efficacy was rated as 'excellent' during four surgical procedures (three major, one minor) and 'moderate' during one major surgery. Incremental in vivo recovery (IVR) data were comparable with the one-stage and chromogenic assays. IVR was >2.0% per IU kg for all measurements and stable over 6 months. No patients developed FVIII inhibitors and there were no treatment-related serious or severe adverse events.
These results in adult PTPs indicate that human-cl rhFVIII is effective for the prevention and treatment of bleeds in adults with severe haemophilia A.
Nuwiq[人细胞系衍生重组凝血因子VIII（人源细胞系重组FVIII）]是新一代的重组FVIII蛋白，未经过化学修饰，也未与任何其他蛋白融合，由人细胞系生产。
目的/方法：这项前瞻性、开放标签、多中心III期研究评估了人源细胞系重组FVIII在32例曾接受治疗的重度A型血友病成年患者（PTPs）中进行≥6个月且暴露天数≥50天的标准预防治疗时的疗效和安全性。还评估了其在治疗出血和手术预防中的疗效。
基于平均每月出血率的预防疗效，在所有出血情况中，97%的患者被评为“优秀”或“良好”，在自发性出血情况中，100%的患者被评为“优秀”或“良好”。所有出血的平均（标准差）年化出血率为2.28（3.73）[中位数=0.9]，自发性出血为1.16（2.57）[中位数=0]，创伤性出血为1.00（1.79）[中位数=0]。50%的患者未发生出血，也没有严重的、危及生命的出血。在治疗的28次出血中，28次（100%）的疗效为“优秀”或“良好”。在4次外科手术（3次大手术、1次小手术）期间，总体疗效被评为“优秀”，在1次大手术期间被评为“中等”。体内增量回收率（IVR）数据与一期和发色底物法检测结果相当。所有测量的IVR均>2.0%/IU·kg，且在6个月内保持稳定。没有患者产生FVIII抑制剂，也没有与治疗相关的严重或重度不良事件。
这些在成年PTPs中的结果表明，人源细胞系重组FVIII对预防和治疗重度A型血友病成年患者的出血有效。
