Iclusig获准用于某些白血病患者

圣路易斯(MD Consult)——2012年12月14日，美国食品药品管理局(FDA)和阿瑞雅德制药公司(Ariad Pharmaceuticals)宣布Iclusig(ponatinib)已被加速批准用于对此前酪氨酸激酶抑制剂(TKI)治疗耐药或不耐受的成年慢性期、加速期或急变期粒细胞性白血病(CML)患者。Iclusig还同时获准用于对此前TKI治疗耐药或不耐受的成年费城染色体阳性急性淋巴细胞性白血病(Ph+ALL)。Iclusig是唯一被证明具有对抗BCR-ABL T315I管家基因突变活性的TKI，这是一种最常见的突变，大约10%的耐药患者发生该突变。

Iclusig获得FDA批准是基于2项针对449例对此前TKI治疗耐药或不耐受的CML或Ph+ALL患者的关键2期试验结果。所有受试者均接受Iclusig治疗，Iclusig显示出强有力的抗白血病活性，54%的慢性期CML患者(70%为T315I突变携带者)获得主要细胞遗传学应答。

临床试验期间报告的最常见不良反应包括高血压、皮疹、腹痛、疲乏、头痛、皮肤干燥、便秘、发热、关节痛以及恶心。血液学不良反应包括血小板减少、贫血、中性粒细胞减少、淋巴细胞减少和白细胞减少。

一些Iclusig治疗患者发生了心血管、脑血管和外周血管血栓形成，包括致命性心梗和卒中。8%的Iclusig治疗患者发生严重动脉血栓形成。应建议发生动脉血栓形成事件患者间断给药和考虑停止用药。Iclusig的获批附带了一项黑框警告，警示患者或医护人员该药物可导致血栓形成和肝脏毒性。

Iclusig推荐剂量为1片(45 mg)/次，1次/d，可与食物同服。Iclusig将在约2周内开始向美国患者出售。

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ST LOUIS (MD Consult) - On December 14, 2012, the US Food and Drug Administration (FDA) and Ariad Pharmaceuticals announced the accelerated approval of for the treatment of adults with chronic, accelerated, or blast phase myeloid leukemia (CML) that is resistant or intolerant to prior tyrosine kinase inhibitor (TKI) therapy. Iclusig is also approved for the treatment of adults with Philadelphia chromosome positive acute lymphoblastic leukemia (Ph+ALL) that is resistant or intolerant to prior TKI therapy. Iclusig is the only TKI that demonstrates activity against the T315I gatekeeper mutation of BCR-ABL, the most common mutation occurring in approximately 10% of patients with drug resistance.

The FDA approval of Iclusig was granted on the basis of results from a pivotal phase 2 trial of 449 patients with CML or Ph+ALL who were resistant or intolerant to prior TKI therapy, or who demonstrated the T315I mutation of BCR-ABL. All participants were treated with Iclusig. Iclusig showed robust antileukemic activity, with 54% of patients with chronic-phase CML, including 70% of patients with the T315I mutation, achieving a major cytogenetic response.

The most common adverse effects reported during clinical trials include hypertension, rash, abdominal pain, fatigue, headache, dry skin, constipation, pyrexia, arthralgia, and nausea. Hematologic adverse reactions included thrombocytopenia, anemia, neutropenia, lymphopenia, and leukopenia.

Cardiovascular, cerebrovascular, and peripheral vascular thrombosis, including fatal myocardial infarction and stroke have occurred in Iclusig-treated patients. Serious arterial thrombosis occurred in 8% of Iclusig-treated patients. Dose interruption and consideration for discontinuation should be given for patients who experience arterial thrombotic events. Iclusig is being approved with a Boxed Warning alerting patients and health care professionals that the drug can cause thrombosis and liver toxicity.

The recommended dose of Iclusig is one 45-mg tablet taken once daily with or without food. Iclusig will be available to patients in the United States within approximately 2 weeks of Ariad's announcement through a number of select specialty pharmacies.