美国FDA 3月10日宣布批准Unituxin (dinutuximab)作为高风险神经母细胞瘤患儿综合治疗方案（包括手术、化疗、放射治疗）中的一线治疗药物。
神经母细胞瘤是未成熟神经细胞演变成的一种罕见肿瘤，通常始发于肾上腺，也可能发作于腹部、胸部或临近脊柱的神经组织，常见于小于5岁的儿童。根据美国国立癌症研究所的统计，神经母细胞瘤在儿童中的发病率为1/100000，在男孩中相对常见一些。美国每年有新确诊神经母细胞瘤患者约650例。如果给予积极治疗，这类患者中40%~50%有长期生存的机会。
Unituxin是一种抗体药物，可以结合在神经母细胞瘤细胞的表面，此次被批准为神经母细胞瘤综合治疗方案中的一线药物，适用于对既往综合治疗方案至少产生部分应答的神经母细胞瘤患者。
美国FDA药品评价和研究中心血液疾病和肿瘤产品办公室主任Richard Pazdur博士表示：“Unituxin 是FDA批准的首个特异性针对高风险神经母细胞瘤患者的治疗药物，可在一定程度上满足高风险神经母细胞瘤儿童延长存活期的需求”。
Unituxin的安全性和疗效在一项涉及226例高风险神经母细胞瘤患儿的临床试验中得到证实。 这些患儿的肿瘤在接受了骨髓移植、多药化疗和手术后缩小或消失。受试者随机接受维甲酸、异维A酸、Unituxin+IL-2+GM-CSF。治疗后3年， Unituxin联合用药组中63%的患者存活和无肿瘤生长或复发，异维甲酸组为46%。在最新的生存分析中，Unituxin联合用药组存活比例为73%，异维甲酸组为58%。
Unituxin的药品标签中附有黑框警告，提示患者和卫生保健人员Unituxi会刺激神经细胞，从而导致严重疼痛并需要使用静脉麻醉药品治疗，Unituxi还可能会发生导致神经损伤和危及生命的注射反应，包括上呼吸道肿胀、呼吸困难、低血压。Unituxin的其他严重副作用包括感染、眼科问题、电解质异常和骨髓抑制。
Unituxin最常见的副作用包括严重疼痛、发热、低血小板计数、输注反应、低血压、低钠血症、肝酶升高、贫血、呕吐、腹泻、低钾血症、毛细血管渗漏综合征、中性粒细胞减少和淋巴细胞减少、荨麻疹和低钙血症。
FDA曾授予Unituxin优先审评和孤儿药资格。与此同时， FDA还给United Therapeutics公司颁发了“罕见儿科疾病药物优先审评”的证书，这样以来，United公司下面提交的一个原本不符合优先审评条件的儿科新药申请将可获得优先审评资格。这是FDA自实施罕见儿科疾病优先审评证书项目以来颁发出的第2张证书，旨在鼓励针对某些罕见儿科疾病的药物开发。
FDA Approves Unituxin™ (dinutuximab) for the Treatment of Pediatric High-Risk Neuroblastoma
SILVER SPRING, Md. and RESEARCH TRIANGLE PARK, N.C., March 10, 2015 /PRNewswire/ -- United Therapeutics Corporation (NASDAQ: UTHR) announced today that the United States Food and Drug Administration (FDA) has approved Unituxin™ (dinutuximab) Injection (formerly called ch14.18), in combination with granulocyte-macrophage colony-stimulating factor (GM-CSF), interleukin-2 (IL-2), and 13-cis-retinoic acid (RA), for the treatment of pediatric patients with high-risk neuroblastoma who achieve at least a partial response to prior first-line multiagent, multimodality therapy. Neuroblastoma is the most common extracranial solid cancer in childhood and the most common cancer in infancy, with an annual incidence in the United States of approximately 700 patients, of whom 50% are diagnosed as having high-risk disease. Unituxin is a chimeric biologic antibody that induces cell lysis of GD2-expressing cells through antibody-dependent cell-mediated cytoxicity (ADCC) and complement-dependent cytoxicity (CDC) and is part of an immunotherapeutic regimen to treat pediatric high-risk neuroblastoma.
The approval was based on demonstration of improved event-free survival (EFS) and overall survival (OS) in a multicenter, open-label, randomized trial (ANBL0032) conducted by the Children's Oncology Group (COG). The trial randomized (1:1) 226 patients to either the Unituxin/13-cis-retinoic acid (RA) arm or the RA alone arm. Patients in each arm received six cycles of treatment. The Unituxin/RA arm consisted of Unituxin in combination with granulocyte macrophage-colony stimulating factor and RA (cycles 1, 3, and 5), Unituxin in combination with interleukin-2 and RA (cycles 2 and 4), and RA (cycle 6). Patients were 11 months to 15 years of age (median age 3.8 years).
The major efficacy outcome measure was investigator-assessed EFS, defined as the time from randomization to the first occurrence of relapse, progressive disease, secondary malignancy, or death. At the seventh interim analysis, an improvemen |
