近日，美国食品和药物管理局(FDA)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。
“大约25%到30%的AML患者FLT3基因会发生突变。这些突变与一种特别具有侵略性的疾病形式有关，而且复发的风险更高，”FDA的肿瘤学中心主任Richard Pazdur医学博士说“Xospata便是以这种基因为靶点，是首个获准单独用于治疗FLT3突变AML患者的药物，通常这种类患者复发或对初始治疗没有太大的反应。
批准日期：2018年11月28日 公司：安斯泰来
XOSPATA（富马酸吉列替尼[gilteritinib]）片剂，用于口服
美国最初批准：2018年
作用机制
Gilteritinib是一种抑制多种受体酪氨酸激酶的小分子，包括FMS样酪氨酸激酶3（FLT3）。Gilteritinib证明了在外源表达FLT3的细胞中抑制FLT3受体信号传导和增殖的能力，包括FLT3-ITD，酪氨酸激酶结构域突变（TKD）FLT3-D835Y和FLT3-ITD-D835Y，并且它在表达FLT3-ITD的白血病细胞中诱导细胞凋亡。
适应症和用法
XOSPATA是一种激酶抑制剂，适用于治疗患有FLT3复发或难治性急性髓性白血病（AML）的成年患者
通过FDA批准的测试检测到的突变。
剂量和给药
每日一次口服120mg。
剂量形式和强度
片剂：40毫克。
禁忌症
对gilteritinib或任何赋形剂过敏。在临床试验中观察到过敏反应。
警告和注意事项
•后部可逆性脑病综合征（PRES）：在发生PRES的患者中停用XOSPATA。
•延长QT间期：中断并减少QTcF>500毫秒的住院患者的XOSPATA剂量。在XOSPATA给药之前和期间纠正低钾血症或低镁血症。
•胰腺炎：中断并减少患胰腺炎的患者的剂量。
•胚胎 - 胎儿毒性：当施用于孕妇时，XOSPATA会对胎儿造成伤害。建议胎儿的潜在风险并使用有效的避孕措施。
不良反应
最常见的不良反应（≥20％）为肌痛/关节痛，转氨酶升高，疲劳/不适，发热，非感染性腹泻，呼吸困难，水肿，皮疹，肺炎，恶心，口腔炎，咳嗽，头痛，低血压，头晕和呕吐。
要报告疑似不良反应，请致电1-800-727-7003联系AstellasPharma US，Inc。或致电1-800-FDA-1088或www.fda.gov/medwatch联系FDA。
药物相互作用
•组合P-gp和强CYP3A诱导剂：避免同时使用。
•强CYP3A抑制剂：考虑替代疗法。如果无法避免同时使用强CYP3A抑制剂，则更频繁地监测患者的XOSPATA不良反应。
用于特定人群
哺乳期：建议女性不要母乳喂养。
包装提供/存储和处理
如何提供
XOSPATA（gilteritinib）40毫克片剂以浅黄色圆形薄膜包衣片剂的形式提供，其上印有Astellas标志，同一侧为“235”。 XOSPATA平板电脑有以下包装尺寸：
•装有儿童防护装置的90片装瓶，（NDC 0469-1425-90）
存储
将XOSPATA片剂储存在20ºC至25ºC（68°F至77°F）; 允许的偏差在15ºC到30ºC（59°F到86°F）之间[见USP受控室温]。 保存在原始容器中。
完整说明资料附件：
https://www.accessdata.fda.gov/drugsatfda_docs/label/2018/211349s000lbl.pdf
FDA approves treatment for adult patients who have relapsed or refractory acute myeloid leukemia (AML) with a certain genetic mutation
The U.S. Food and Drug Administration today approved Xospata (gilteritinib) tablets for the treatment of adult patients who have relapsed or refractory acute myeloid leukemia (AML) with a FLT3 mutation as detected by an FDA-approved test. The FDA also approved an expanded indication for a companion diagnostic, to include use with Xospata. The LeukoStrat CDx FLT3 Mutation Assay, developed by Invivoscribe Technologies, Inc., is used to detect the FLT3 mutation in patients with AML.
“Approximately 25 to 30 percent of patients with AML have a mutation in the FLT3 gene. These mutations are associated with a particularly aggressive form of the disease and a higher risk of relapse,” said Richard Pazdur, M.D., director of the FDA’s Oncology Center of Excellence and acting director of the Office of Hematology and Oncology Products in the FDA’s Center for Drug eva luation and Research. “Xospata targets this gene and is the first drug to be approved that can be used alone in treating patients with AML having a FLT3 mutation who have relapsed or who don’t respond to initial treatment.”
AML is a rapidly progressing cancer that crowds out normal cells in the bone marrow and bloodstream, resulting in low numbers of normal blood cells and a continuous need for transfusions. The National Cancer Institute estimates that approximately 19,520 people will be diagnosed with AML this year; approximately 10,670 patients with AML will die of the disease in 2018.
The efficiency of Xospata was studied in a clinical trial of 138 patients with relapsed or refractory AML having a confirmed FLT3 mutation. Twenty-one percent of patients achieved complete remission (no evidence of disease and full recovery of blood counts) or complete remission with partial hematologic recovery (no evidence of disease and partial recovery of blood counts) with treatment. Of the 106 patients who required red blood cell or platelet transfusions at the start of treatment with Xospata, 31 percent became transfusion-free for at least 56 days.
Common side effects reported by patients in clinical trials were muscle and joint pain (myalgia/arthralgia), fatigue and elevated liver enzymes (liver transaminase). Health care providers are advised to monitor patients for posterior reversible encephalopathy syndrome (a syndrome characterized by headache, confusion, seizures and visual loss), prolonged QT interval (a heart rhythm condition that can potentially cause fast, chaotic heartbeats) and pancreatitis (inflammation in the pancreas). Rare cases of differentiation syndrome (symptoms of which may include fever, cough, trouble breathing, fluid around the lungs or heart, rapid weight gain, swelling, and renal or hepatic dysfunction) have been seen in patients taking Xospata. Women who are pregnant or breastfeeding should not take Xospata because it may cause harm to a developing fetus or newborn baby.
The FDA granted this application Fast Track and Priority Review designation. Xospata also received Orphan Drug designation, which provides incentives to assist and encourage the development of drugs for rare diseases.