Pegylated, full-length, recombinant factor VIII for prophylactic and on-demand treatment of severe hemophilia A
Pegylated, full-length, recombinant factor VIII for prophylactic and on-demand treatment of severe hemophilia A
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DOI：
10.1182/blood-2015-03-630897
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发表时间：
2015-08-27
期刊：
影响因子：
20.3
通讯作者：
Abbuehl, Brigitt
中科院分区：
文献类型：
--
作者：
Konkle, Barbara A.;Stasyshyn, Oleksandra;Abbuehl, Brigitt
目前对A型血友病的管理包括每2至3天更换一次因子VIII （FVIII）进行预防。BAX855， Baxalta的聚乙二醇全长重组FVIII (rFVIII)，旨在延长半衰期，从而减少预防性输注的频率，同时保持止血效果。BAX 855在既往治疗的12至65岁严重血友病A患者中进行了评估。一项i期研究比较了BAX855与获批的rFVIII （Advate）的药代动力学（PK）特征。在一项关键研究中，评估了年化出血率（ABR）、PK参数和出血治疗的疗效。在1期研究中，BAX 855的平均半衰期（T-1/2）和平均停留时间比Advate高1.4- 1.5倍。这些结果在关键研究中得到证实。关键研究达到了其主要终点：BAX 855预防导致ABR显著低于按需治疗ABR的一半（P < 0.0001）。中位ABR为1.9,39.6%的依从性受试者在预防期间没有出血发作，而按需治疗的受试者的中位ABR为41.5。BAX855对出血发作的治疗也有效，1 ~ 2次输注的出血发作率为95.9%，96.1%的疗效评分为优/良。未发现FVIII抑制抗体或安全信号。这些研究提供的证据表明，BAX855对于血友病A患者按需治疗和预防是安全有效的，每周给予两次。
Current management of hemophilia A includes prophylaxis with factor VIII (FVIII) replacement every 2 to 3 days. BAX855, Baxalta's pegylated full-length recombinant FVIII (rFVIII), was designed to increase half-life and, thus, reduce the frequency of prophylactic infusions while maintaining hemostatic efficacy. BAX 855 was evaluated in previously treated patients with severe hemophilia A who were aged 12 to 65 years. A phase 1 study compared the pharmacokinetic (PK) profile of BAX855 with that of licensed rFVIII (Advate). In a pivotal study, the annualized bleeding rate (ABR), PK parameters, and efficacy of bleeding treatment were assessed. In the phase 1 study, the mean half-life (T-1/2) and the mean residence time of BAX 855 compared with Advate were 1.4- to 1.5-fold higher. These results were confirmed in the pivotal study. The pivotal study met its primary endpoint: Prophylaxis with BAX 855 resulted in an ABR that was significantly lower than half the ABR of on-demand treatment (P < .0001). The median ABR was 1.9, and 39.6% of compliant subjects had no bleeding episodes during prophylaxis, whereas subjects treated on-demand had a median ABR of 41.5. BAX855 was also efficacious for the treatment of bleeding episodes, with 95.9% of bleeding episodes treated with 1 to 2 infusions and 96.1% having efficacy ratings of excellent/good. No FVIII inhibitory antibodies or safety signals were identified. These studies provide evidence that BAX855 was safe and efficacious for on-demand treatment and prophylaxis administered twice weekly in patients with hemophilia A.