新型因子VIII(FVIII)抑制剂Hemlibra(emicizumab-kxwh)—20年来首个获美国FDA批准.

2017年11月16日，美国FDA批准新治疗为预防或减少在有因子VIII抑制剂血友病A患者出血发作的频数。美国食品和药品监管局今天批准Hemlibra(emicizumab-kxwh)预防或减少出血发作的频数在成年和儿童患者有血友病A患者已发生抗体被称为因子VIII (FVIII)抑制剂。
FDA的药品评价和研究中心中血液学和肿瘤产品办公室代理主任和FDA的肿瘤卓越中心主任Richard Pazdur，M.D说：“对有血友病患者.减少频数或预防出血发作是疾病处理中一个重要部分今天的批准提供一个新预防性治疗，在有因子VIII抑制剂有血友病A患者中曽被显示显著地减少出血发作数量，” “此外，用Hemlibra治疗的患者报告他们的身体功能改善。”
血友病A是一种遗传的血液-凝固疾患主要影响男性。按照美国国立卫生院，生在美国每5,000男性血友病影响一人，他们约80 %有血友病A。有血友病A患者是缺失一个基因它产生因子VIII，一种能使血液凝固的蛋白质。患者可能经受重复严重出血的发作，主要地至他们的关节，其结果可能是被严重地受损。有些患者发生一种免疫反应被称为一个FVIII抑制剂或抗体。抗体干扰对血友病当前可得到的治疗的有效性。
Hemlibra是一种第一流的治疗方，通过在血液中桥接其他因子来恢复这些患者的血液凝结。Hemlibra是一种每周预防性治疗通过在皮下注射。
Hemlibra的安全性和疗效是根据两项临床试验的数据。第一个试验包括109例男性年龄12岁和以上有FVIII抑制剂血友病A。试验的随机化部分比较Hemlibra与无预防性处理在53例患者，他们在以前被用按-需求治疗在纳入试验中前用一个旁路[bypassing]药。患者服用Hemlibra经历约2.9次治疗出血发作每年相比较约23.3次治疗出血发作每年对患者没有接受预防性处理。这个代表一个87%减低在治疗出血率中。试验还包括2-报告的生活质量对身体健康指标。用Hemlibra治疗患者与未接受预防性处理患者比较报告在血友病相关症状一个改善(疼痛的肿胀和关节痛)和身体功能(疼痛与运动和走路困难)。第二个试验是一项23例年龄12岁以下有有FVIII抑制剂血友病A单臂试验。在该试验期间，87%的用Hemlibra患者没有经受一次需要治疗的出血发作。
Hemlibra的常见副作用包括注射部位反应，头痛，和关节痛。
对Hemlibra说明书含一个黑框警告警戒卫生保健专业人员和患者也给予救援治疗(活化的凝血酶原复合物浓缩物)患者当服用Hemlibra治疗出血共24小时或以上曽观察到严重血凝块(血栓性微血管病和血栓栓塞)。
FDA授权这个申请优先审评和突破性治疗指定。Hemlibra还接受孤儿药物指定，它提供奖励帮助和鼓励对罕见疾病药物的开发。
FDA授权Hemlibra的批准给予Genentech，有限公司。
Hemlibra Approved to Treat Hemophilia A With Inhibitors
Genentech announced that the Food and Drug Administration (FDA) has approved Hemlibra (emicizumab-kxwh) injection for routine prophylaxis to prevent or reduce the frequency of bleeding episodes in patients with hemophilia A with factor VIII inhibitors.
Hemlibra, a bispecific factor IXa- and factor X-directed antibody, brings together factors IXa and X proteins; they are required to activate the natural coagulation cascade and restore the clotting process for hemophilia A patients.
The Phase 3 randomized, open-label HAVEN 1 study enrolled 109 patients aged ≥12 years with hemophilia A with inhibitors. Patients who received Hemlibra prophylaxis experienced a statistically significant reduction in treated bleeds by 87% (95% CI: 72.3, 94.3; P<00001) vs. patients who did not receive prophylaxis.
In addition, findings from an intra-patient analysis revealed Hemlibra prophylaxis statistically and significantly reduced treated bleeds of 79% (95 CI: 51.4, 91.1; P=0.0003) vs. previous treatment with bypassing agent (BPA) prophylaxis collected in a non-interventional study before enrollment. 
The single-arm, open-label HAVEN 2 study enrolled patients <12 years with hemophilia A with inhibitors. The data showed 87% of those who received Hemlibra prophylaxis had zero treated bleeds. An intra-patient analysis (n=13) showed a 99% reduction in treated bleeds with Hemlibra prophylaxis vs. previous treatment with BPA prophylaxis or on-demand.
Pooled safety data showed injection site reactions, headache, and arthralgia as the most common adverse events (≥10% occurrence).
“This new medicine has been shown to reduce the frequency of bleeds compared to the currently available medicines and only needs to be injected once a week. This could make a meaningful difference for these children,” said Guy Young, MD, director of Hemostasis and Thrombosis Program, Children's Hospital Los Angeles, CA.
Hemlibra will be available as 30mg/mL, 60mg/0.4mL, 105mg/0.7mL, and 150mg/mL strengths in single-dose vials in the near future.
https://www.fda.gov/NewsEvents/Newsroom/PressAnnouncements/ucm585567.htm