英文药名：Alecensa(Alectinib Capsules)

中文药名：阿雷替尼胶囊（别名 艾乐替尼）

生产厂家：美国基因泰克公司
药品简介
新型肺癌药物ALECENSA(ALECTINIB HYDROCHLORIDE)CAPSULE ORAL获FDA批准上市
近日，美国食品和药物管理局（FDA）已授予口服靶向抗癌药Alecensa（alectinib）第2个突破性药物资格（BTD），用于之前未接受ALK抑制剂治疗的晚期间变性淋巴瘤激酶（ALK）阳性非小细胞肺癌（NSCLC）成人患者。Alecensa是一种ALK抑制剂，之前，FDA于2013年首次授予该药突破性药物资格，用于既往接受辉瑞口服靶向抗癌药Xalkori（crizotinib，克唑替尼）治疗后病情进展的ALK阳性NSCLC患者。
批准日期：2016年10月6日 公司：Genentech
ALECENSA(阿雷替尼  alectinib)胶囊，为口服使用
美国初次批准：2015
作用机制
Alectinib是一种酪氨酸激酶抑制剂靶向ALK和RET。在非临床研究，alectinib抑制ALK磷酸化和ALK-介导的下游信号蛋白STAT3和AKT的激活，和在窝藏ALK 融合，扩增，或激活突变多种细胞系减低肿瘤细胞活力。Alectinib的主要活性代谢物，M4，显示相似体外效力和活性。Alectinib和M4显示体外和体内对多种ALK酶突变型，包括有些用克里唑蒂尼已进展患者NSCLC肿瘤内鉴定的突变体，在移植携带ALK融合肿瘤的小鼠模型中，给予alectinib导致抗肿瘤活性和延长生命，包括颅内植入来自有ALK-肿瘤细胞系小鼠模型。
适应证和用途
ALECENSA是一个激酶抑制剂适用为的治疗有间变性淋巴瘤激酶(ALK)-阳性，转移非小细胞肺癌(NSCLC)进展对或是对克里唑蒂尼耐受的患者的治疗。这个适应证是在加快审批下被批准根据肿瘤反应率和反应时间。继续批准这个适应证可能取决于在验证性试验中临床获益的验证和描述。
剂量和给药方法
600mg口服每天2次。与食物给予ALECENSA。
剂型和规格
胶囊：150mg
禁忌证
无。
警告和注意事项
⑴ 肝毒性：监视肝实验室测试每2周治疗的头2个月期间，和任何治疗期间定期。严重ALT，AST，或胆红素升高情况中，不给，然后减低剂量，或永久地终止ALECENSA
⑵间质性肺病(ILD)/肺炎：0.4%患者发生。被诊断ILD/肺炎患者立即不给ALECENSA和如已确定没有ILD/肺炎的其他潜在原因永久地终止。
⑶心动过缓：常规地监视心率和血压。如症状性，不给ALECENSA然后减低剂量，或永久地终止。
⑷严重肌痛和肌酸磷酸激酶(CPK)升高：发生分别在1.2%和4.6%患者。治疗的头一个月期间每2周评估CPK和在患者报告不解释肌痛，触痛，或乏力。在严重CPK升高情况中，不给，然后恢复或减低剂量。
⑸胚胎胎儿毒性：ALECENSA可能致胎儿危害。忠告有生殖潜能女性对胎儿潜在风险和使用有效避孕。
不良反应
最常见不良反应(发生率≥20%)是疲乏，便秘，水肿和肌痛。
特殊人群中使用
哺乳：不要哺乳喂养。
包装/贮存和处置
硬胶囊，白色150mg胶囊在帽上黑墨汁印有“ALE”和体上印有“150mg”，可得到以下：
240胶囊每瓶：NDC 50242-130-01
贮存和稳定性：不要贮存30°C(86°F)以上。贮存在原始容器避光和潮湿保护。

完整资料附件：https://dailymed.nlm.nih.gov/dailymed/drugInfo.cfm?setid=42c49deb-713b-427a-9670-08af08adcffb

FDA grants Roche's Alecensa (alectinib) accelerated approval for people with a specific type of lung cancer
US Food and Drug Administration (FDA) granted accelerated approval to Alecensa® (alectinib) for the treatment of people with anaplastic lymphoma kinase (ALK)-positive, metastatic non-small cell lung cancer (NSCLC) who have progressed on or are intolerant to crizotinib. In the pivotal studies, Alecensa shrank tumours in up to 44 percent of people with ALK-positive NSCLC who progressed on crizotinib (objective response rate [ORR] of 38 percent [95 percent CI 28-49] and 44 percent [95 percent CI 36-53]).
In a subset of people with tumours that spread to the brain or other parts of the central nervous system (CNS), Alecensa shrank CNS tumours in about 60 percent of people (CNS ORR of 61 percent [95 percent CI 46-74]).
“Alecensa is now approved as a new option for people with ALK-positive NSCLC who progress on or are intolerant to crizotinib,” said Sandra Horning, M.D., Chief Medical Officer and Head of Global Product Development. “Sixty percent of people enrolled in our studies had tumours that had spread to their central nervous systems, and Alecensa shrank tumours in many people in a subset of patients with CNS disease.”
Possible serious side effects with Alecensa include liver problems, lung problems, slow heartbeat, muscle pain, tenderness and weakness. The most common side effects of Alecensa include tiredness, constipation and swelling in the hands, feet, ankles and eyelids.
The FDA’s Accelerated Approval Program allows conditional approval of a medicine that fills an unmet medical need for a serious condition based on early evidence suggesting clinical benefit.
The indication for Alecensa is approved under accelerated approval based on tumour response rate and duration of response (DOR). Continued approval for this indication may be contingent upon verification and description of clinical benefit in confirmatory trials.
In addition, Alecensa is being studied for use as an initial (first-line) treatment for people with advanced ALK-positive NSCLC. ALEX is a global, randomised phase III study comparing Alecensa to crizotinib as an initial treatment for people with advanced NSCLC whose tumours were characterised as ALK-positive by a companion VENTANA ALK (D5F3) CDx Assay immunohistochemistry (IHC) test developed by Roche Diagnostics.
This study is part of the company’s commitment to convert the current accelerated approval in people with ALK-positive, metastatic NSCLC who have progressed on or are intolerant to crizotinib to a full approval as an initial treatment.
About NP28761 (Study 1) and NP28673 (Study 2)
Study 1 is a phase II North American, single-arm, open-label, multicentre trial evaluating the safety and efficacy of Alecensa (600 mg orally twice daily) in 87 people with ALK-positive NSCLC whose disease progressed on crizotinib. Study 2 is a phase I/II global, single-arm, open-label, multicentre trial evaluating the safety and efficacy of Alecensa (600 mg orally twice daily) in 138 people with ALK-positive NSCLC whose disease progressed on crizotinib. People in the phase II studies received 600 mg of Alecensa orally twice daily.
In both trials, the primary endpoint was ORR according to Response Evaluation Criteria in Solid Tumours (RECIST v1.1), as evaluated by an Independent Review Committee (IRC). Secondary endpoints included DOR and efficacy against disease that had spread to the CNS (CNS ORR and CNS DOR). A summary of the efficacy and safety data from both studies that support this approval is included below.

The most common Grade 3 or higher adverse events in the pooled analysis of both studies were an increase in muscle enzymes (creatine phosphokinase; 4.6 percent), shortness of breath (dyspnea; 3.6 percent), increased liver enzymes (aspartate transaminase; 3.6 percent, and alanine transaminase; 4.8 percent), evidence of liver dysfunction (hyperbilirubinemia; 2.4 percent), increased blood glucose (hyperglycemia; 2 percent), decreased levels of minerals (hypokalemia; 4 percent, hypophosphatemia; 2.8 percent, and hyponatremia; 2 percent), decreased red blood cells (anemia; 2 percent) and decreased white blood cells (lymphopenia; 4.6 percent).
About Alecensa
Alecensa (RG7853/AF-802/RO5424802/CH5424802) is an investigational oral medicine created at Chugai and is being developed for people with NSCLC whose tumours are identified as ALK+. ALK+ NSCLC is often found in younger people who have a light or non-smoking history.
It is almost always found in people with a specific type of NSCLC called adenocarcinoma.
Early studies with Alecensa have shown activity on brain metastases, indicating that the drug may be taken up in the brain.
The brain is protected by the Blood-Brain Barrier, a network of tightly joined cells that line the inside of the blood vessels in the brain and spinal cord. One of the ways the Blood-Brain Barrier prevents molecules from affecting the brain is to actively eject them from the barrier through a process known as active efflux.
The active efflux system does not recognise Alecensa, which means that it may travel into and throughout brain tissue.
The Global phase III studies of Alecensa include a companion test developed by Roche.
Alecensa is marketed in Japan by Chugai Pharmaceutical, a member of the Roche Group.
About Roche in lung cancer
Lung cancer is a major area of focus and investment for Roche, and we are committed to developing new approaches, medicines and tests that can help people with this deadly disease. Our goal is to provide an effective treatment option for every person diagnosed with lung cancer. We currently have two approved medicines to treat certain kinds of lung cancer and more than ten medicines being developed to target the most common genetic drivers of lung cancer or to boost the immune system to combat the disease.