2015年3月10日,美国食品和药品监管局(FDA)批准Unituxin(dinutuximab)注射作为对有高风险神经母细胞瘤儿童患者一线治疗的一部分,一类癌症大多数往往发生在年青儿童。 神经母细胞瘤是一种罕见癌,来自神经细胞形成。它通常开始在肾上腺但还可能在腹部,胸或临近脊柱神经组织。 神经母细胞瘤典型地发生在小于5岁幼童。按照美国国家癌症研究所,神经母细胞瘤发生在约1/100,000儿童和在男孩略微更常见。在美国每年估计被诊断神经母细胞瘤650新病例。尽管积极的治疗有高风险神经母细胞瘤患者有40至50%长期生存的机会。 Unituxin是一种抗体结合至神经母细胞瘤细胞的表面。Unituxin正在被批准作为多模式方案,包括手术,化疗和放疗为对以前多药物,多模式一线治疗实现至少部分缓解患者治疗的一个部分。 美国FDA药品评价和研究中心血液学和肿瘤产品室主任Richard Pazdur,M.D.说:“Unituxin 标记第一个批准为一种治疗目标特异性地针对有高风险神经母细胞瘤患者的治疗,”“Unituxin满足提供一种治疗选择延长有高风险神经母细胞瘤儿童活存至关重要的选择。” FDA授权Unituxin优先审评和孤儿产品指定。优先审评与标准审评比较缩短药物申请审评时间限4个月,而优先审评授予药物,如被批准,将提供在某种严重情况的治疗中安全性和有效性显著改进。孤儿产品指定是给予药物意向治疗罕见病,与这个批准FDA还发出一个罕见儿科疾病优先审评证件至United Therapeutics公司,提供优先审评至一个随后药物申请本来没资格优先审评。这是自从罕见儿科疾病审评证件程序开始以来FDA授予的第二个罕见儿科疾病优先审评证件,它是被设计鼓励对某些罕见儿科疾病的预防和治疗新治疗发展。 在226例小儿有高风险神经母细胞瘤参加者一项临床试验评价Unituxin的安全性和疗效,在用多-药化疗治疗和手术接着通过另外加强化疗和患儿随后接受骨髓移植支持和放射治疗后其肿瘤皱缩或消失。参加者被随机赋予接受或一个口服维甲酸药物[retinoid drug],异维A酸[isotretinoin](RA),或Unituxin与白介素-2和粒细胞 - 巨噬细胞集落刺激因子联用,被认为Unituxin通过刺激免疫系统,和RA增强活性。 治疗赋予后三年,63%参加者接受Unituxin联用活存和无肿瘤生长或复发,与之比较单独用RA治疗参加者46%。在一个更新的生存分析中,接受Unituxin联用73%参加者活存与之比较单独接受 RA参加者58 %。 Unituxin携带一个黑框警告警戒患者和卫生保健专业人员Unituxin刺激神经细胞,致严重疼痛需要治疗用静脉麻醉药品和还可能致神经损伤和危及生命输注反应,包括上呼吸道肿胀,呼吸困难,和低血压,输注期间或完成后短期。Unituxin还可能致其他严重副作用包括感染,眼问题,电解质异常和骨髓抑制。 Unituxin的最常见副作用是严重疼痛,发热,低血小板计数,输注反应,低血压,血中盐低水平(低钠血症),升高的肝酶,贫血,呕吐,腹泻,血中低钾水平,毛细血管渗漏综合征(其特征为血浆和其他血组分从血管的大量渗漏进入临近体腔和肌肉),低数量的感染斗争的白血细胞(中性粒细胞减少和淋巴细胞减少),荨麻疹,和低血钙水平。. Unituxin是由总部在马里兰Silver Spring,United Therapeutics公司上市。 http://www.fda.gov/NewsEvents/Newsroom/PressAnnouncements/ucm437460.htm New Drugs Online Report for dinutuximab Generic Name: dinutuximab Trade Name: Unituxin Synonym: ch14.18 Entry Type: New molecular entity Development and Regulatory status UK: Pre-registration (Filed) EU: Pre-registration (Filed) US: Approved (Licensed) UK launch Plans: Available only to registered users Actual UK launch date: Comments Mar 15: FDA approves dinutuximab to treat paediatric patients with high-risk cases of neuroblastoma [4]. 10/03/2015 17:14:52 Orphan drug status in the EU (EU/3/11/879) and the US [2]. 03/02/2014 14:16:41 Jan 14: Filed in the EU [1]. 03/02/2014 14:15:59 Trial or other data Preliminary results from a PIII trial of dinutuximab in combination with interleukin-2 and sargramostim being conducted by the National Cancer Institute were published in the New England Journal of Medicine in September 2010 (ANBL0032; NCT00026312). The proportion of children with neuroblastoma who were alive and free of disease progression after two years was 46% for those on a standard therapy and 66% for children on dinutuximab. The Children´s Oncology Group and the NCI are conducting a PIII trial of dinutuximab in combination with sargramostim, aldesleukin, and isotretinoin after autologous stem cell transplantation in 105 patients with high risk neuroblastoma (NCT01041638) [2]. 03/02/2014 14:21:22 Evidence Based Evaluations NHSC/NIHR http://www.hsc.nihr.ac.uk/topics/dinutuximab-unituxin-for-high-risk-neuroblastoma-a/ References Available only to registered users Category BNF Category: Other immunomodulating drugs (08.02.04) Pharmacology: Monoclonal antibody targeting GD2, an glycolipid found on the surface of tumour cells, which is overexpressed in neuroblastoma Epidemiology: Neuroblastoma affects approximately 100 children each year in the UK and usually affects children under the age of five . An estimated 40% of neuroblastoma patients are classified as high-risk. Indication: Neuroblastoma Additional Details: high-risk children and adolescents (≤21 years) Method(s) of Administration Intravenous Company Information Name: United Therapeutics Limited US Name: United Therapeutics Limited Further Information Anticipated commissioning route (England) NHSE High cost drug list? Awaiting Update Implications Available only to registered users |