2018年11月29日，美国食品和药物管理局（FDA）已批准Xospata（gilteritinib），用于经FDA批准的一种检测方法证实存在FLT3突变的复发性或难治性（药物难治）急性髓性白血病（AML）成人患者的治疗。Xospata是一种口服疗法，此次批准，使该药成为FDA批准用于复发性或难治性AML患者群体的首个也是唯一一个FLT3靶向制剂，同时也标志着安斯泰来进入了美国血液癌症治疗领域。
  据美国癌症协会估计，在2018年，美国将有大约1.9万人被诊断为AML。AML与多种基因突变有关。Xospata属于第二代FLT3抑制剂，针对FLT3跨膜区内部串联重复（ITD）和FLT3酪氨酸激酶结构域（TKD）这2种不同的突变具有抑制作用。FLT3-ITD突变影响约30%的AML患者，与恶化的无病生存和总体生存相关。FLT3-TKD突变影响约7%的AML患者。尽管对这些突变的影响还不太清楚，但它们与治疗耐药性有关。
  之前，FDA已授予Xospata孤儿药资格和快速通道资格，并被日本卫生劳动福利部（MHLW）和欧盟委员会（EC）授予孤儿药资格，被日本MHLW授予SAKIGAKE资格。今年10月中旬，Xospata获得日本批准，用于FLT3突变阳性复发性或难治性AML成人患者。
Xospata是通过与日本寿制药株式会社（Kotobuki Pharmaceutical）的研究合作发现，安斯泰来拥有开发、制造、潜在商业化Xospata的独家全球权利。
  FDA批准Xospata是基于ADMIRAL临床研究中下列终点的中期分析：完全缓解率（CR）/伴部分血液学恢复的完全缓解（CRh），CR/CRh缓解持续时间（DOR），依赖输血向不依赖输血的转化率。数据显示，CR/CRh为21%、CR/CRh的中位DOR为4.6个月。基线期后56天，从依赖输血向不依赖输血的转化率为31.1%。
  来自ADMIRAL研究的全部结果将在即将召开的医学会议上公布。
  值得一提的是，2017年4月，诺华的靶向抗癌药Rydapt（midostaurin）获FDA批准，治疗FLT3突变阳性新诊AML成人患者。此次批准，使Rydapt成为全球首个一线治疗FLT3突变阳性AML的靶向药物。
HIGHLIGHTS OF PRESCRIBING INFORMATION
These highlights do not include all the information needed to use
XOSPATA safely and effectively. See full prescribing information for
XOSPATA.
XOSPATA® (gilteritinib) tablets, for oral use
Initial U.S. Approval: 2018
INDICATIONS AND USAGE
XOSPATA is a kinase inhibitor indicated for the treatment of adult patientswho have relapsed or refractory acute myeloid leukemia (AML) with a FLT3mutation as detected by an FDA-approved test. (1.1)
DOSAGE AND ADMINISTRATION
120 mg orally once-daily. (2.2)
DOSAGE FORMS AND STRENGTHS
Tablet: 40 mg. (3)
CONTRAINDICATIONS
Hypersensitivity to gilteritinib or any of the excipients. Anaphylactic reactionshave been observed in clinical trials. (4, 6.1)
WARNINGS AND PRECAUTIONS
•Posterior reversible encephalopathy syndrome (PRES): DiscontinueXOSPATA in patients who develop PRES. (2.3, 5.1, 6.1)
•Prolonged QT Interval: Interrupt and reduce XOSPATA dosage inpatients who have a QTcF >500 msec. Correct hypokalemia orhypomagnesemia prior to and during XOSPATA administration. (2.3,5.2, 12.2, 6.1)
•Pancreatitis: Interrupt and reduce the dose in patients who developpancreatitis. (2.3, 5.3)
Embryo-Fetal Toxicity: XOSPATA can cause fetal harm when
administered to a pregnant woman. Advise of the potential risk to a fetusand to use effective contraception. (5.4, 8.1, 8.3)
ADVERSE REACTIONS
The most common adverse reactions (≥20%) were myalgia/arthralgia,transaminase increase, fatigue/malaise, fever, noninfectious diarrhea, dyspnea,edema, rash, pneumonia, nausea, stomatitis, cough, headache, hypotension,dizziness and vomiting. (6.1)
To report SUSPECTED ADVERSE REACTIONS, contact AstellasPharma US, Inc. at 1-800-727-7003 or FDA at 1-800-FDA-1088 orwww.fda.gov/medwatch.
DRUG INTERACTIONS
•Combined P-gp and Strong CYP3A Inducers: Avoid concomitant use.(7.1)
•Strong CYP3A Inhibitors: Consider alternative therapies. If theconcomitant use of strong CYP3A inhibitors cannot be avoided, monitorpatients more frequently for XOSPATA adverse reactions. (2.3, 7.1)
USE IN SPECIFIC POPULATIONS
Lactation: Advise women not to breastfeed. (8.2)
See 17 for PATIENT COUNSELING INFORMATION and FDAapprovedpatient la