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FDA批准Rydapt(midostaurin)为首个急性髓性白血病（AML）靶向新药

2017-05-05 01:59:54 作者：新特药房来源：互联网浏览次数：2 文字大小：【大】【中】【小】

简介： 首个急性髓性白血病靶向新药:midostaurin(商品名 Rydapt)被FDA批准用于联合化疗一线治疗携带FLT3突变的新确诊成人急性髓性白血病2017年4月28日，FDA批准诺华Rydapt(midostaurin)，用于联合化疗一线治疗携 ...

关键字：midostaurin商品名Rydapt 靶向新药用于治疗急性髓性白血病

首个急性髓性白血病靶向新药:midostaurin(商品名 Rydapt)被FDA批准用于联合化疗一线治疗携带FLT3突变的新确诊成人急性髓性白血病
2017年4月28日，FDA批准诺华Rydapt(midostaurin)，用于联合化疗一线治疗携带FLT3突变的新确诊成人急性髓性白血病。FDA同时批准了Invivoscribe Technologies公司的伴随诊断试剂盒LeukoStrat CDx FLT3。
AML是一种快速进展的血液和骨髓肿瘤，发病率随年龄的增大而明显升高，中位发病年龄为66岁。在美国的AML中，适合接受骨髓移植的患者不足10%，而且大多数患者对化疗无响应并且会进展成复发或难治性AML，5年生存率大约20%~25%。根据美国癌症研究所的估计，2016年美国大约有19930例新确诊AML患者，10430例死亡AML患者。
FLT3突变是AML患者中一种常见的基因突变，与患者预后较差相关。midostaurin是一种口服多激酶抑制剂，可抑制多种调控细胞生长的关键激酶，包括Flt3，因此被开发用于携带FTL3突变的急性髓性白血病（AML）患者的治疗，是首个用于治疗AML的靶向药物。FDA还批准Rydapt用于治疗罕见血液疾病（侵袭性全身性肥大细胞增多症）。
FDA曾授予midostaurin优先审评、快速通道（肥大细胞增多症）和突破性药物资格（AML）。一项代号为RATIFY的随机研究入组了717例初治AML患者，结果显示，与仅接受化疗的患者相比，Rydapt联合化疗可显著延长患者的生存期（74.7 vs 25.6个月）。
Rydapt治疗AML的常见不良反应包括白细胞减少、恶心、黏膜炎、呕吐、头痛、皮肤瘀点、肌肉骨骼疼痛、鼻出血、高血糖、上呼吸道感染
midostaurin(商品名 Rydapt)的推荐计量为:50亳克，一天二次口服，在化疗周期的第8-21天；化疗结束后，继续每天50毫克口服，共12个月。
包装规格：
胶囊剂
25毫克*56、112粒/瓶
完整处方信息：https://www.fda.gov/NewsEvents/Newsroom/PressAnnouncements/ucm555778.htm
General Information
Rydapt(midostaurin) is a multikinase inhibitor.
Rydapt is specifically indicated for the following:
•in combination with standard cytarabine and daunorubicin induction and cytarabine consolidation chemotherapy, for the treatment of adult patients with newly diagnosed acute myeloid leukemia (AML) who are FLT3 mutationpositive, as detected by a FDA approved test
•for the treatment of adult patients with aggressive systemic mastocytosis (ASM), systemic mastocytosis with associated hematological neoplasm (SM-AHN), or mast cell leukemia
Rydapt is supplied as a capsule for oral administration. Recommended Dosage in Acute Myeloid Leukemia: 50 mg orally twice daily with food on Days 8 to 21 of each cycle of induction with cytarabine and daunorubicin and on Days 8 to 21 of each cycle of consolidation with high-dose cytarabine. Recommended Dosage in ASM, SM-AHN, and MCL: 100 mg orally twice daily with food. Continue treatment until disease progression or unacceptable toxicity occurs.
Please see drug label for recommendations for dose modifications in patients with ASM, SM-AHN, and MCL. Monitor patients for toxicity at least weekly for the first 4 weeks, every other week for the next 8 weeks, and monthly thereafter while on treatment.
Mechanism of Action
Rydapt (midostaurin) is a small molecule that inhibits multiple receptor tyrosine kinases. In vitro biochemical or cellular assays have shown that midostaurin or its major human active metabolites CGP62221 and CGP52421 inhibit the activity of wild type FLT3, FLT3 mutant kinases (ITD and TKD), KIT (wild type and D816V mutant), PDGFRα/β, VEGFR2, as well as members of the serine/threonine kinase PKC (protein kinase C) family. Midostaurin demonstrated the ability to inhibit FLT3 receptor signaling and cell proliferation, and it induced apoptosis in leukemic cells expressing ITD and TKD mutant FLT3 receptors or overexpressing wild type FLT3 and PDGF receptors. Midostaurin also demonstrated the ability to inhibit KIT signaling, cell proliferation and histamine release and induce apoptosis in mast cells.