4月29日，美国FDA批准Zykadia(ceritinib)用于治疗晚期转移性非小细胞肺癌 (NSCLC)。Zykadia是一种间变性淋巴瘤激酶(ALK) 酪氨酸激酶抑制剂，它可以阻断促癌蛋白。这款药物适用于之前接受过克唑替尼（Crizotinib）治疗的转移性 ALK阳性NSCLC患者，克唑替尼是仅有的另一款ALK酪氨酸激酶抑制剂。 肺癌是因癌死亡的主要因素。根据美国国家癌症研究所提供的信息，今年美国预计有22.421万人将被确诊为肺癌，有15.92万人将死于这种疾病。大约85%的肺癌是NSCLC，这使其成为最常见的肺癌类型。然而，只有2-7% 的NSCLC患者其ALK呈阳性。 Zykadia 是第四款以突破性治疗药物资格获得FDA批准的药物。它比这款药物的处方药用户付费目标日期 2014年8月24日相比，提前4个月获得批准，后者是FDA计划完成药物申请审评的预期日期。 FDA授予Zykadia突破性治疗药物资格，优先审评及孤儿药资格，因为这款药物的申请者通过初步临床试验证据证明这款药物可能会提供一种相对现有治疗药物的实质性改善；这款药物在其申请提交时，在一种严重疾病治疗的安全性或有效性方面可能有显著改善，并且这款药物旨在治疗一种罕见疾病。 Zykadia的安全性及有效性基于一项由163名转移性ALK阳性NSCLC受试者参与的临床试验。所有受试者均以 Zykadia治疗。结果显示，大约50%的受试者其肿瘤缩小，这种效果平均持续了大约7个月。 Zykadia的常见副作用包括消化道症状，如腹泻、恶心、呕吐和腹痛。肝酶增加、胰酶及葡萄糖水平增加等实验室异常也有被观察到。Zykadia由诺华上市销售。 Zykadia (ceritinib) is a highly selective inhibitor of anaplastic lymphoma kinase (ALK). ALK is a key gene implicated in the development of some lung cancers. Zykadia is specifically indicated for the treatment of patients with anaplastic lymphoma kinase (ALK)-positive metastatic non-small cell lung cancer who have progressed on or are intolerant to crizotinib. Zykadia is supplied as a capsule (150 mg) for oral administration. The recommended initial dose is 750 mg orally once daily. Administer Zykadia on an empty stomach. ZYKADIA Rx Generic Name and Formulations: Ceritinib 150mg; hard gel caps. Company: Novartis Pharmaceuticals Corp Indications for ZYKADIA: Treatment of patients with anaplastic lymphoma kinase (ALK)-positive metastatic non-small cell lung cancer (NSCLC) who have progressed on or are intolerant to crizotinib. Not established for improvement in survival or disease-related symptoms. Adult: Take on an empty stomach (at least 2 hours before or after a meal). 750mg once daily until disease progression or unacceptable toxicity. Discontinue if 300mg once daily not tolerated. Moderate-to-severe hepatic impairment: not established. Dose modifications: see full labeling. If concomitant use of strong CYP3A4 inhibitors unavoidable: reduce ceritinib dose by 1/3. Children: Not established. Warnings/Precautions: Monitor for severe or persistent GI toxicity; if occurs, withhold until improved; resume at reduced dose. Monitor ALT/AST and total bilirubin once monthly, and more frequently if elevated transaminases develop; withhold then reduce dose, or permanently discontinue as clinically indicated. Congenital long QT syndrome; avoid. Patients with CHF, bradyarrhythmias, electrolyte abnormalities, or those who are taking drugs known to prolong the QTc interval; monitor ECG, electrolytes periodically. Permanently discontinue if QTc prolongation in combination with Torsade de pointes or polymorphic ventricular tachycardia or serious arrhythmia develop. Monitor HR and BP regularly; fasting serum glucose, lipase, amylase prior to initiation and periodically thereafter. Monitor for pulmonary symptoms as clinically indicated. Permanently discontinue if treatment-related interstitial lung disease (ILD)/pneumonitis, uncontrolled hyperglycemia, or life-threatening bradycardia occur. Pregnancy (Cat.D). Females of reproductive potential should use effective contraception during treatment and for at least 2 weeks after completion. Nursing mothers: not recommended. Interactions: See Adults. Potentiated by strong CYP3A4 inhibitors (eg, ritonavir, macrolides, ketoconazole, nefazodone), grapefruit juice; avoid. Avoid concomitant strong CYP3A4 inducers (eg, carbamazepine, phenytoin, rifampin, St. John’s Wort). Avoid concomitant CYP3A substrates (eg, alfentanil, cyclosporine, ergots, fentanyl, pimozide, quinidine, sirolimus, tacrolimus) or CYP2C9 substrates (eg, phenytoin, warfarin) with narrow therapeutic indices; if unavoidable, reduce doses of these drugs. Avoid concomitant agents known to cause bradycardia (eg, beta-blockers, non-dihydropyridine CCBs, clonidine, digoxin). Pharmacological Class: Tyrosine kinase inhibitor. Adverse Reactions: Diarrhea, nausea, vomiting, abdominal pain, constipation, elevated transaminases, fatigue, decreased appetite; bradycardia, hepatotoxicity, ILD/pneumonitis, QTc prolongation, hyperglycemia, pancreatitis. How Supplied: Caps—70 Zykadia (Ceritinib) Treatment of Metastatic Non-Small Cell Lung Cancer (NSCLC), United States of America Zykadia (Ceritinib / LDK378) is an inhibitor of anaplastic lymphoma kinase (ALK) indicated for treatment of non-small cell lung cancer (NSCLC). The drug was discovered and developed by Novartis Pharmaceuticals and approved by the US Food and Drug Administration (FDA) for treating ALK-positive metastatic NSCLC patients following treatment with Crizotinib in April 2014. The Committee for Medicinal Products for Human Use (CHMP) of EMA adopted positive opinion for granting conditional marketing authorisation for Zykadia for the treatment of adult patients with ALK positive advanced NSCLC in February 2015. In May 2015, the European Commission (EC) approved the drug for the same indication in the European Union (EU). Non-small cell lung cancer drug Non-small cell lung cancer (NSCLC) is the most common type of cancer that accounts for approximately 85% of all lung cancers and is the leading cause of cancer-related deaths worldwide. The disease occurs when abnormal cells rapidly multiply and don't stop reproducing. Zykadia mechanism of action Zykadia contains an ALK inhibitor that works against the ALK gene involved in development of cancers. The drug is available in 150mg gelatin capsules for oral administration. Clinical trials on Zykadia Phase II clinical trials on Zykadia were conducted between July 2005 and October 2007. The open label, non-randomised and parallel assignment enrolled 85 patients with NSCLC. The primary outcome measure of the study was clinical efficacy based on the evaluation of objective tumour response rate (RR). The secondary outcome measures included assessment of the safety of RAD001 monotherapy, additional clinical efficacy of RAD001 and the steady state levels of RAD001 in blood, and to investigate potential molecular markers predictive of clinical effect. Novartis initiated another Phase II clinical trial on Zykadia in April 2012. The open label, multi-centre, interventional and parallel assignment enrolled 83 patients. The primary outcome measure of the study was frequency and characteristics of dose limiting toxicities (DLTs) in 28 days, whereas the secondary outcome measures included overall survival (OS), frequency, duration and severity of adverse events (AEs), progression-free survival (PFS) and plasma concentration of INC280. FDA-approval for Zykadia was based on results obtained from a pivotal phase III clinical trial. It was a single-arm, open-label study that enrolled 163 subjects with metastatic ALK-positive NSCLC, who progressed while receiving or were intolerant to Crizotinib. Patients were administered with Zykadia at a dose of 750mg once-daily. The study enrolled patients with a median age of 52 years. The most common sites of metastases evaluated in the clinical study included brain, liver and bone. Results of the study demonstrated that the patients who were treated with Zykadia achieved an overall response rate (ORR) of 54.6% and a median duration of response (DOR) of 7.4 months. The most common adverse reaction found in the Zykadia-administered patients during the clinical study included diarrhoea, nausea, elevated transaminases, vomiting, abdominal pain, fatigue, decreased appetite and constipation. Safety and efficacy of Zykadia were evaluated in Study 1, which enrolled 304 patients, with 255 of these treated with Zykadia doses ranging between 50mg and 750mg. The results of the study demonstrated that approximately 96% of the 255 patients who were treated with Zykadia experienced diarrhoea, nausea, vomiting or abdominal pain. The study also found that drug-induced hepatotoxicity occurred in patients treated with Zykadia. The Study 1 further found that about 3% of the 255 patients experienced a QTc interval increase over baseline greater than 60msec. Pneumonitis was reported in 4% of 255 patients treated with Zykadia, while sinus bradycardia occurred in 1% of 255 patients treated with Zykadia. The EC's approval of Zykadia was based on the data obtained from two clinical trials known as ASCEND-1 and ASCEND-2, which were open-label, single-arm, global and multicentre studies. The ASCEND-1 study enrolled 246 ALK+NSCLC patients, whereas the ASCEND-2 study enrolled 140 patients with locally advanced or metastatic ALK+ NSCLC. The results of the ASCEND-1 demonstrated that the patients who were administered with Zykadia 750mg daily after previous treatment with chemotherapy, followed by an ALK inhibitor, experienced ORR of 56.4%, the median DOR was 8.3 months, and the median PFS was 6.9 months. The most common adverse reactions found in both of the clinical studies in the patients treated with Zykadia included diarrhoea, nausea, vomiting, tiredness, abdominal pain, decreased appetite, constipation, rash, heartburn and anaemia. Trade Name：Zykadia Generic Name：ceritinib Synonym：LDK378 Chemical Name:5-Chloro-N2-[2-isopropoxy-5-methyl-4-(4-piperidinyl)phenyl]-N4-[2-(isopropylsulfonyl)phenyl]-2,4-pyrimidinediamine CAS number：1032900-25-6 Mechanism of Action:Anaplastic lymphoma kinase inhibitor Clinical Trail Data:among 163-treated patients, Zykadia achieved an overall response rate (ORR) of 54.6% and a median duration of response (DOR) of 7.4 months Dosage and Administration:750 mg orally once daily Date of Approval: April 29, 2014 Indication：ALK positive non-small cell lung cancer (ALK+ NSCLC) Company:Novartis Pharmaceuticals Corporation https://dailymed.nlm.nih.gov/dailymed/drugInfo.cfm?setid=fff5d805-4ffd-4e8e-8e63-6f129697563e 肺癌突破性口服药物Zykadia(ceritinib)获欧洲批准上市 2015年5月11日，诺华针对间变性淋巴瘤激酶阳性（ALK+）转移性非小细胞肺癌（NSCLC）患者的治疗药物Zykadia获得了欧洲药品管理局的批准，而一年之前美国就已经批准了该药物。 欧洲药品管理局批准Zykadia(ceritinib)用于治疗间变性淋巴瘤激酶阳性（ALK+）转移性非小细胞肺癌（NSCLC），这类患者病情已经恶化或对辉瑞的Xalkori (crizotinib)不耐受。针对这部分患者，Zykadia(ceritinib)将成为首选治疗药物。 这项批准决定主要是基于两个全球性、多中心、非盲单组临床实验结果。第一个名为ASCEND-1的试验A结果显示，给药的患者整体反应率（肿瘤缩小）为56.4%。而试验B（ASCEND-2）的数据将会在即将到来的一个医学会议上公布。 每年全球共有160万患者被诊断出肺癌，其中非小细胞肺癌(NSCLC）占比85%-90%，而这之中2%-7%的病例是由ALK基因重排导致的，ALK基因能够与其他基因融合，表达一种异常的融合蛋白，促进癌细胞的形成和生长。 针对这类患者，Xalkori是目前的标准治疗方式，然而不是所有患者都对Xalkori治疗有反应，一些患者病情会继续发展，这就迫切需要新的治疗药物。 此前一项针对接受过Xalkori治疗的 163名间变性淋巴瘤激酶阳性（ALK+）转移性非小细胞肺癌（NSCLC）患者的临床试验结果表明，患者使用Zykadia后整体反应率达到了54.6%，中位生存期达到了7.4个月。基于该试验结果，Zykadia获得了美国的加速批准。 ------------------------------------------------ 产地国家：美国 原产地英文商品名: Zykadia capsules 150mg/capsule 700capsules/box 原产地英文药品名: CERITINIB 中文参考商品译名: Zykadia硬胶囊 150毫克/胶囊 70胶囊/盒 中文参考药品译名: 色瑞替尼 生产厂家中文参考译名: 诺华 生产厂家英文名: Novartis ------------------------------------------------ 产地国家：德国 原产地英文商品名: Zykadia capsules 150mg/capsule 150capsules/box(3bottlesx50) 原产地英文药品名: CERITINIB 中文参考商品译名: Zykadia硬胶囊 150毫克/胶囊 150胶囊/盒（3瓶*50粒） 中文参考药品译名: 色瑞替尼 生产厂家中文参考译名: 诺华 生产厂家英文名: Novartis ------------------------------------------------ 产地国家：瑞士 原产地英文商品名: Zykadia capsules 150mg/capsule 150capsules/box(3bottlesx50) 原产地英文药品名: CERITINIB 中文参考商品译名: Zykadia硬胶囊 150毫克/胶囊 150胶囊/盒（3瓶*50粒） 中文参考药品译名: 色瑞替尼 生产厂家中文参考译名: 诺华 生产厂家英文名: Novartis ------------------------------------------------ 产地国家：日本 原产地英文商品名: Zykadia capsules 150mg/capsule 14capsules/box 原产地英文药品名: CERITINIB 中文参考商品译名: Zykadia硬胶囊 150毫克/胶囊 14胶囊/盒 中文参考药品译名: 色瑞替尼 生产厂家中文参考译名: 诺华 生产厂家英文名: Novartis