针对间变性淋巴瘤激酶(ALK)阳性的非小细胞肺癌的最新靶向治疗药物alectinib (Alecensa)首次获日本批准。该抗肿瘤药将由罗氏制药的分公司Chugai推向日本市场，并于今年晚些时候正式面市。
辉瑞（Pfizer）抗癌药物克唑替尼（赛可瑞, Crizotinib, xalkori) 是首个ALK阳性非小细胞肺癌的靶向治疗药物，2011年8月在美国获批。从那以后，在美国又有另一种特异性靶向抗肿瘤药被批准用于这类患者的治疗。2014年4月，FDA提前批准罗氏的Zykadia (ceritinib, 色瑞替尼)用于以前应用克里唑蒂尼治疗过的、ALK阳性非小细胞肺癌患者的治疗。
日本卫生部、劳动和福利局批准该抗肿瘤药是基于在日本进行的I期和II期AF-001JP临床试验的积极结果，该研究达到了缓解率大于90%的主要终点。罗氏公司指出，正在进行中的临床试验结果将用于世界其他地区的申请。Chugai还将与罗氏另一个分公司Ventana医疗合作进行alectinib的 全球性III期试验。
上述在日本的试验涉及晚期、复发或不能切除的、已经应用过至少一种化疗方案的、ALK阳性非小细胞肺癌患者。该试验分为两个部分。I期试验包括24 位患者，评估了上述抗肿瘤药的安全性、耐受性和药动学参数，确定了推荐剂量（300mg口服，一天2次）。II期试验包括46位患者，评估了推荐剂量的疗效和安全性。在该研究中，alectinib组患者的缓解率为93.5%。此外，12个月时患者的无进展生存率为83%。
Synthesis of Alectinib (Alecensa, アレクチニブ) – Roche’s Breakthrough-Designated Lung Cancer Drug
Alectinib (trade Name:Alecensa, also known as CH5424802,RO5424802), a second generation oral inhibitor of anaplastic lymphoma kinase (ALK), is being developed by Chugai and Roche for the treatment of patients with ALK-positive non-small cell lung cancer (NSCLC) that has progressed on Xalkori (Crizotinib). On July 4, 2014 , Japan became the first country to approve Roche’s alectinib (trade Name:Alecensa®, 一般名:アレクチニブ,  商品名：アレセンサ), which was given a green light by Japan’s Ministry of Health Labour and Welfare to treat non-small cell lung cancer (NSCLC) patients who test positive for the anaplastic lymphoma kinase (ALK) fusion gene, which is commonly referred to as ALK+ NSCLC.
Alectinib was discovered by Chugai Pharmaceutical Co. Ltd. Chugai became a subsidiary of Roche in 2002 and the Swiss group currently owns 59.9 percent of the company.
On October 8, 2013, Chugai Pharmaceutical announced that it has filed a new drug application to Japan’s Ministry of Health, Labour and Welfare (MHLW) for alectinib hydrochloride for the treatment of ALK fusion gene positive non-small cell lung cancer (NSCLC).
Pfizer’s Xalkori (Crizotinib, 赛可瑞, 克唑替尼), a first-in-class ALK tyrosine kinase inhibitor, received accelerated approval from the FDA in 2011 for ALK-positive non-small cell lung cancer (NSCLC).Unfortunately, despite the initial responses of crizotinib, most patients develop acquired resistance to crizotinib.
The second generation ALK inhibitors entering the clinic have primarily been studied in ALK-positive NSCLC patients who have acquired resistance to crizotinib.The most advanced of these are Zykadia (Ceritinib, LDK378 , Novartis), alectinib (Roche) and AP26113 (Ariad).
Zykadia (Ceritinib, LDK378, 色瑞替尼) was approved on April 29, 2014, 4 months ahead of schedule by the U.S. Food and Drug Administration (FDA) for the treatment of patients with ALK-positive metastatic non-small cell lung cancer (NSCLC) following treatment with crizotinib (Xalkori).
On June 26, 2013, The U.S. Food and Drug Administration (FDA) has granted breakthrough therapy designation for alectinib based on data that was presented at European Cancer Congress (ECC) in Amsterdam between September 27 to October 1, 2013. The investigational second-generation ALK inhibitor alectinib produced objective responses in 54.5% of patients with ALK-positive non–small cell lung cancer refractory to crizotinib in a phase I dose-finding study. Alectinib has already demonstrated an objective response rate of 93.5% in crizotinib (Xalkori)-naive ALK-positive non–small cell lung cancer.
Synthesis of Alectinib Hydrochloride (アレクチニブ塩酸塩, Alecensa) – Roche’s Trade Name: Alecensa, アレセンサ
Generic Name:Alectinib, アレクチニブ, アレクチニブ塩酸塩
Synonym:AF802,RG7853,CH5424802,RO5424802
Chemical Name: 9-Ethyl-6,11-dihydro-6,6-dimethyl-8-[4-(4-morpholinyl)-1-piperidinyl]-11-oxo-5H-benzo[b]carbazole-3-carbonitrile
Chemical Name in Chinese: 9-乙基-6,11-二氢-6,6-二甲基-8-[4-(4-吗啉基)-1-哌啶基]-11-氧代-5H-苯并[B]咔唑-3-甲腈
CAS Number:1256580-46-7 (Alectinib),  1256589-74-8 (Alectinib Hydrochloride)
Mechanism of Action:ALK inhibitor
Indication:Non-small cell lung cancer (NSCLC)
Current Status:Phase II (US,EU,UK), NDA(Japan)
Company:中外製薬株式会社 (Chugai), Roche