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美国FDA批准Defitelio(去纤维钠）为骨髓干细胞移植新药

2016-03-31 07:47:31 作者：新特药房来源：互联网浏览次数：5 文字大小：【大】【中】【小】

简介： 2016年3月30日美国食品和药品监管局(FDA)批准Defitelio (去纤维钠[defibrotide sodium])治疗接受一个来自血或骨髓干细胞移植被称为造血干细胞移植(HSCT)后发生肝小静脉闭塞病(VOD)有另外肾或肺异常成年和 ...

关键字：去纤维钠 defibrotidesodium 商品名defitelio 干细胞移植肝合并症优先审评孤儿药物

2016年3月30日美国食品和药品监管局(FDA)批准Defitelio (去纤维钠[defibrotide sodium])治疗接受一个来自血或骨髓干细胞移植被称为造血干细胞移植(HSCT)后发生肝小静脉闭塞病(VOD)有另外肾或肺异常成年和儿童。这是第一个FDA-批准的治疗为严重肝VOD，一种罕见和危及生命肝脏情况的治疗。
HSCT是在有些患者治疗某些血或骨髓癌进行的一个过程。一个HSCT过程前立即，某个患者接受化疗。在接受化疗和HSCT患者中可能发生肝VOD。肝VOD是一种情况其中肝脏有些静脉成为被阻断，引起肝脏内肿胀和血流减低，它可能导致肝损伤。肝VOD的最严重形式，患者可能还发生肾和肺衰竭。较少与2 %患者HSCT后发生严重肝VOD，但多至80 %患者发生严重肝VOD不能生存。
FDA的药品评价和研究中心中血液学和肿瘤室主任Richard Pazdur，M.D.说：“批准满足移植社会接受化疗和HSCT患者治疗这个罕见但频繁致命性合并症显著需求。”
在三项研究在 528例被治疗患者研究Defitelio的疗效：两项前瞻性临床试验和一项延伸评估研究。在纳入所有三项研究的患者HSCT后有一个肝VOD与肝或肾异常的诊断。研究测量HSCT后100天仍活着患者的百分率(总体生存)。在三项研究中，HSCT后100天38至45%用Defitelio治疗患者为活着。根据发表的报道和患者-等级数据的分析，HSCT后100天，对有严重肝VOD患者仅接受支持医护或除了Defitelio外其他干预。预期生存率将是21至31%。
Defitelio的最常见副作用包括异常地低血压，腹泻，呕吐，恶心和鼻出血。Defitelio的严重潜在副作用已被确定的包括出血和过敏反应。有出血合并症或正在用薄血药或减低机体形成凝固能力的其他药物的患者不应使用Defitelio。
鉴于有严重或危及生命情况患者它们的潜在获益，FDA授权申请优先审评状态，促进和加快某些药物的发展和审评。Defitelio还接受孤儿药物指定，它提供鼓励例如税收减免，用户费用减免和专有权资格以帮助和鼓励对罕见病药物的开发。
Defitelio是由总部在加州Palo Alto的Jazz制药上市。
Defitelio Approved to Treat Hepatic Veno-Occlusive Disease
The U.S. Food & Drug Administration has approved Defitelio (defibrotide sodium; Jazz Pharmaceuticals) for the treatment of hepatic veno-occlusive disease (VOD), also known as sinusoidal obstruction syndrome (SOS), with renal or pulmonary dysfunction following hematopoietic stem cell transplantation (HSCT) in adult and pediatric patients. The application for defibrotide sodium was granted Priority Review by the FDA; this designation is given to drugs that treat a serious condition.
The efficacy of defibrotide sodium was evaluated in 528 patients in two prospective clinical trials and an expanded access study. The patients enrolled had a diagnosis of hepatic VOD with multi-organ dysfunction after transplantation. They received defibrotide sodium 6.25mg/kg IV every 6 hours until resolution of VOD. Approval was based on survival at Day +100 after HSCT. The Day +100 survival rates for Study 1, Study 2 and Study 3 were 38% (95% CI: 29%, 48%), 44% (95% CI: 33%, 55%) and 45% (95% CI: 40%, 51%) respectively. Based on published reports and analyses of patient-level data, the Day + 100 survival rates were 21–31% for patients with hepatic VOD with renal or pulmonary dysfunction who received supportive care or interventions other than defibrotide sodium.
The mechanism of action of defibrotide sodium has not been fully elucidated. In vitro, defibrotide sodium enhances the enzymatic activity of plasmin to hydrolyze fibrin clots. Studies evaluating the pharmacological effects of defibrotide sodium on endothelial cells (ECs) were conducted primarily in the human microvascular endothelial cell line. In vitro, defibrotide sodium increased tissue plasminogen activator (t-PA) and thrombomodulin expression, and decreased von Willebrand factor (vWF) and plasminogen activator inhibitor-1 (PAI-1) expression, thereby reducing EC activation and increasing EC-mediated fibrinolysis. Defibrotide sodium protected ECs from damage caused by chemotherapy, tumor necrosis factor-α (TNF-α), serum starvation, and perfusion.
The use of defibrotide sodium is contraindicated in patients being treated concurrently with anticoagulants or fibrinolytic therapies. Hemorrhage and hypersensitivity reactions are the major potential adverse reactions. The most common adverse reactions (incidence greater than or equal to 10%) were hypotension, diarrhea, vomiting, nausea, and epistaxis.
Defitelio is supplied in a single-use vial for intravenous infusion; each vial contains 200mg/2.5mL of defibrotide sodium.