Division of Hematology/Oncology, School of Medicine, University of California at Davis, Davis, California, USA.
Thromb Haemost. 2012 Nov;108(5):913-22. doi: 10.1160/TH12-03-0188. Epub 2012 Sep 26.
The benefits of prophylaxis of haemophilia A patients regarding joint health and quality-of-life are well established. However, adherence to an up to every-other-day infusion regimen is a barrier to widespread adoption of prophylaxis. BAY 79-4980 is an investigational drug consisting of rFVIII-FS (sucrose-formulated recombinant FVIII) reconstituted with liposome solvent. Previous clinical studies showed extended protection from bleeding after a single injection of BAY 79-4980 (13.3 ± 6.2 days) compared with rFVIII-FS (7.2 ± 1.7 days). The effect of once-a-week prophylaxis with BAY 79-4980 (35 IU/kg) compared with three times-per-week rFVIII-FS (25 IU/kg) in previously treated, severe haemophilia A patients was evaluated in a 52-week, double-blind, two-arm, randomised, controlled study. The primary and secondary endpoints were protection from total bleeds and joint bleeds, respectively. Short- and long-term safety and tolerability of BAY 79-4980 including effects on lipid levels were assessed. A total of 139 and 131 subjects were evaluable for safety and efficacy analyses, respectively. A large difference in efficacy between treatment groups was observed with 72.1% (49/68) in the rFVIII-FS control group demonstrating <9 bleeds/year compared with 38.1% (24/63) of BAY 79-4980-treated subjects. A similar difference was seen in annualised joint bleeds, with 43 subjects (63.2%) in the control group demonstrating <5 joint bleeds/year compared with 24 subjects (38.1%) treated with BAY 79-4980. The distribution of bleeds seven days post-prophylactic treatment with BAY 79-4980 showed that 61% of bleeds occurred after day 4 post dosing. There were no safety concerns identified. The investigational treatment arm was prematurely discontinued due to failure to achieve the primary endpoint.
A型血友病患者预防治疗在关节健康和生活质量方面的益处已得到充分证实。然而，每两天一次的输注方案的依从性是广泛采用预防治疗的障碍。BAY 79-4980 是一种研究性药物，由重组 FVIII-FS（蔗糖配方）与脂质体溶剂重新组成。先前的临床研究表明，与 rFVIII-FS（7.2±1.7 天）相比，单次注射 BAY 79-4980 后可延长出血预防时间（13.3±6.2 天）。在先前接受治疗的重度 A 型血友病患者中，每周一次 BAY 79-4980（35IU/kg）与每周三次 rFVIII-FS（25IU/kg）预防治疗的效果在一项为期 52 周、双盲、双臂、随机、对照研究中进行了评估。主要和次要终点分别是总出血和关节出血的预防。评估了 BAY 79-4980 的短期和长期安全性和耐受性，包括对血脂水平的影响。共有 139 名和 131 名受试者分别可用于安全性和疗效分析。治疗组之间的疗效差异很大，rFVIII-FS 对照组中有 72.1%（49/68）的患者年出血率<9 次，而 BAY 79-4980 治疗组中仅有 38.1%（24/63）的患者年出血率<9 次。关节出血年发生率也存在类似的差异，对照组中有 43 名（63.2%）受试者年关节出血<5 次，而接受 BAY 79-4980 治疗的受试者仅有 24 名（38.1%）。BAY 79-4980 预防性治疗后 7 天出血的分布显示，61%的出血发生在给药后第 4 天。未发现安全性问题。由于未能达到主要终点，该研究性治疗组提前停止。
