Tibsovo(Ivosidenib)是一款首创新药。具有选择性、针对IDH1基因突变癌症的强效口服靶向抑制剂。

2018年7月20日,美国食品和药物管理局批准了Tibsovo(ivosidenib)片剂，用于治疗具有特定基因突变的复发或难治性急性髓细胞白血病(AML)的成年患者。这是第一类药物（IDH1抑制剂），并被批准与FDA批准的伴随诊断一起使用，用于检测AML患者IDH1基因的特异性突变。
“Tibsovo是一种有针对性的疗法，它填补了复发或难治性AML患者IDH1突变的未满足的需求，”FDA肿瘤学中心主任、FDA血液学和肿瘤产品办公室代理主任、医学博士Richard Pazdur说。药物评价和研究中心。使用Tibsovo与某些患者的完全缓解以及减少红细胞和血小板输注的需求有关。
  AML是一种在骨髓中形成的快速进展的癌症，导致血液和骨髓中异常白细胞数量的增加。美国国立卫生研究院的国家癌症研究所估计，今年大约有19520人将被诊断为AML，大约有10670名AML患者将在2018年死于该疾病。
  Tibsovo是一种异柠檬酸脱氢酶-1抑制剂，其作用是减少癌代谢物2-羟基戊二酸酯（2-HG）的异常产生，导致恶性细胞的分化。如果通过FDA批准的检测在血液或骨髓样本中检测到IDH1突变，患者就有资格接受Tibsovo治疗。今天，该机构还批准了实时IDH1检测，一个同伴诊断，可以用来检测这种突变。
  对174例复发或顽固性AML伴IDH1突变的成年患者进行单臂试验，研究替布索沃的疗效。该试验测量了没有疾病证据和治疗后血细胞计数完全恢复的患者（完全缓解或CR）以及没有疾病证据和治疗后血细胞计数部分恢复的患者（部分血液学r完全缓解）的百分比。生态或CRH）。中位随访8.3个月，32.8%的患者经历了持续8.2个月的CR ORCRH。在研究开始时由于急性髓细胞白血病需要输血或血小板的110名患者中，37%的患者在接受Tibsovo治疗后至少56天没有输血。
  Tibsovo的常见副作用包括疲劳、白细胞增加、关节疼痛、腹泻、呼吸急促、手臂或腿部肿胀、恶心、口腔或喉咙疼痛或疼痛、不规则心跳（QT延长）、皮疹、发烧、咳嗽和便秘。母乳喂养的妇女不应该服用TBSOVO，因为它可能对新生儿造成伤害。
  TIsSOVO必须分发一个病人用药指南，描述药物使用和风险的重要信息。Tibsovo的处方信息包括盒式警告，称之为分化综合征的不良反应可能发生，如果不治疗，可能致命。辨证的症状和体征可以包括发烧、呼吸困难（呼吸困难）、急性呼吸窘迫、肺部炎症（肺部放射线浸润）、肺部或心脏周围的液体（胸腔或心包积液）、快速体重增加、肿胀（外周eDEMA）或肝（肝）、肾（肾）或多器官功能障碍。一开始怀疑症状，医生应该用皮质类固醇治疗病人，密切监测病人直到症状消失。
  其他严重的警告包括QT延长，这可能危及生命。心脏的电活动应在治疗期间用心电图测试。Guillain-Barré综合征是一种罕见的神经疾病，其中身体的免疫系统错误地攻击其周围神经系统的一部分，发生在接受Tibsovo治疗的人中，因此应该监测患者的神经系统问题。FDA批准了这个应用程序的快速跟踪和优先审查指定。Tibsovo还获得了孤儿药物指定。
FDA批准了阿吉奥斯制药公司的Tibsovo。FDA批准了Abbott实验室的实时IDH1检测。

FDA-approved tibsovo, targeted therapy and relapse/refractory patients in adult acute leukemia with IDH1 mutation myeloid and amphetamine
About TIBSOVO(ivosidenib)
TIBSOVO®(ivosidenib) is an isocitrate dehydrogenase-1 (IDH1) inhibitor indicated for the treatment of adult patients with relapsed or refractory acute myeloid leukemia (AML) with a susceptible IDH1 mutation as detected by an FDA-approved test. For more information, visit TIBSOVO.com.
IMPORTANT SAFETY INFORMATION
WARNING: DIFFERENTIATION SYNDROME
Patients treated with TIBSOVO have experienced symptoms of differentiation syndrome, which can be fatal if not treated. Symptoms may include fever, dyspnea, hypoxia, pulmonary infiltrates, pleural or pericardial effusions, rapid weight gain or peripheral edema, hypotension, and hepatic, renal, or multi-organ dysfunction. If differentiation syndrome is suspected, initiate corticosteroid therapy and hemodynamic monitoring until symptom resolution.
WARNINGS AND PRECAUTIONS
Differentiation Syndrome: See Boxed WARNING. In the clinical trial, 19% (34/179) of patients with relapsed or refractory AML treated with TIBSOVO experienced differentiation syndrome. Differentiation syndrome is associated with rapid proliferation and differentiation of myeloid cells and may be life-threatening or fatal if not treated. Symptoms of differentiation syndrome in patients treated with TIBSOVO included noninfectious leukocytosis, peripheral edema, pyrexia, dyspnea, pleural effusion, hypotension, hypoxia, pulmonary edema, pneumonitis, pericardial effusion, rash, fluid overload, tumor lysis syndrome, and creatinine increased. Of the 34 patients who experienced differentiation syndrome, 27 (79%) recovered after treatment or after dose interruption of TIBSOVO. Differentiation syndrome occurred as early as 1 day and up to 3 months after TIBSOVO initiation and has been observed with or without concomitant leukocytosis.
If differentiation syndrome is suspected, initiate dexamethasone 10 mg IV every 12 hours (or an equivalent dose of an alternative oral or IV corticosteroid) and hemodynamic monitoring until improvement. If concomitant noninfectious leukocytosis is observed, initiate treatment with hydroxyurea or leukapheresis, as clinically indicated. Taper corticosteroids and hydroxyurea after resolution of symptoms and administer corticosteroids for a minimum of 3 days. Symptoms of differentiation syndrome may recur with premature discontinuation of corticosteroid and/or hydroxyurea treatment. If severe signs and/or symptoms persist for more than 48 hours after initiation of corticosteroids, interrupt TIBSOVO until signs and symptoms are no longer severe.
QTc Interval Prolongation: Patients treated with TIBSOVO can develop QT (QTc) prolongation and ventricular arrhythmias. One patient developed ventricular fibrillation attributed to TIBSOVO. Concomitant use of TIBSOVO with drugs known to prolong the QTc interval (e.g., anti-arrhythmic medicines, fluoroquinolones, triazole anti-fungals, 5-HT3 receptor antagonists) and CYP3A4 inhibitors may increase the risk of QTc interval prolongation. Conduct monitoring of electrocardiograms (ECGs) and electrolytes. In patients with congenital long QTc syndrome, congestive heart failure, electrolyte abnormalities, or in those who are taking medications known to prolong the QTc interval, more frequent monitoring may be necessary.
Interrupt TIBSOVO if QTc increases to greater than 480 msec and less than 500 msec. Interrupt and reduce TIBSOVO if QTc increases to greater than 500 msec. Permanently discontinue TIBSOVO in patients who develop QTc interval prolongation with signs or symptoms of life-threatening arrhythmia.
Guillain-Barré Syndrome: Guillain-Barré syndrome occurred in <1% (2/258) of patients treated with TIBSOVO in the clinical study. Monitor patients taking TIBSOVO for onset of new signs or symptoms of motor and/or sensory neuropathy such as unilateral or bilateral weakness, sensory alterations, paresthesias, or difficulty breathing. Permanently discontinue TIBSOVO in patients who are diagnosed with Guillain-Barré syndrome.
ADVERSE REACTIONS
The most common adverse reactions (≥20%) of any grade were fatigue (39%), leukocytosis (38%), arthralgia (36%), diarrhea (34%), dyspnea (33%), edema (32%), nausea (31%), mucositis (28%), electrocardiogram QT prolonged (26%), rash (26%), pyrexia (23%), cough (22%), and constipation (20%).
The most frequently reported ≥Grade 3 adverse reactions (≥5%) were electrocardiogram QT prolonged (10%), dyspnea (9%), leukocytosis (8%), tumor lysis syndrome (6%), and differentiation syndrome (5%).
Serious adverse reactions (≥5%) were differentiation syndrome (10%), leukocytosis (10%), and electrocardiogram QT prolonged (7%). There was one case of progressive multifocal leukoencephalopathy (PML).
DRUG INTERACTIONS
Strong or Moderate CYP3A4 Inhibitors: Reduce TIBSOVO dose with strong CYP3A4 inhibitors. Monitor patients for increased risk of QTc interval prolongation.
Strong CYP3A4 Inducers: Avoid concomitant use with TIBSOVO.
Sensitive CYP3A4 Substrates: Avoid concomitant use with TIBSOVO.
QTc Prolonging Drugs: Avoid concomitant use with TIBSOVO. If co-administration is unavoidable, monitor patients for increased risk of QTc interval prolongation.
LACTATION
Many drugs are excreted in human milk and because of the potential for adverse reactions in breastfed children, advise women not to breastfeed during treatment with TIBSOVO and for at least 1 month after the last dose.
Please see full Prescribing Information, including Boxed WARNING.
About Acute Myelogenous Leukemia (AML)
AML, a cancer of blood and bone marrow characterized by rapid disease progression, is the most common acute leukemia affecting adults.4 Undifferentiated blast cells proliferate in the bone marrow rather than mature into normal blood cells.4 AML incidence significantly increases with age, and the median age of diagnosis is 68.3 The vast majority of patients do not respond to chemotherapy and progress to relapsed/refractory AML.5 The five-year survival rate for AML is approximately 27 percent.3 IDH1 mutations are present in about 6 to 10 percent of AML cases。
1）：https://www.tibsovo.com/
2：https://www.tibsovo.com/pdf/prescribinginformation.pdf
3）：https://dailymed.nlm.nih.gov/dailymed/drugInfo.cfm?setid=5b6d8ae8-bac8-4e1b-b1b4-7f9665e62de5