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新类型抗癌药Cotellic获FDA批准即将上市

2015-11-12 09:07:19 作者：新特药房来源：互联网浏览次数：9 文字大小：【大】【中】【小】

简介： 美国FDA批准Cotellic与vemurafenib的组合治疗晚期黑色色素瘤2015年11月10日,美国食品和药品监管局(FDA)批准Cotellic(cobimetinib)将被使用与威罗菲尼[vemurafenib]联用治疗已播散至几天其他部位或不能用手 ...

关键字：cobimetinib商品名cotellic 联用治疗黑色素瘤优先审评孤儿药物

——美国FDA批准Cotellic与vemurafenib的组合治疗晚期黑色色素瘤
2015年11月10日,美国食品和药品监管局(FDA)批准Cotellic(cobimetinib)将被使用与威罗菲尼[vemurafenib]联用治疗已播散至几天其他部位或不能用手术去除和有某种类型异常基因(BRAF V600E或V600K突变)的晚期黑色素瘤。
黑色素瘤是在美国最侵袭性的和危险的形式皮肤癌。它在发展皮肤色素的皮肤细胞中形成和如果没有早期诊断，癌有可能扩散到身体的其他部位。美国国家癌症研究所估计今年73,870美国人将被诊断有黑色素瘤和9,940例将死于此病。
FDA的药品评价和研究中心中血液学和肿瘤产品室主任Richard Pazdur，M.D.说：“因为我们肿瘤生物学知识的继续进展，我们已学习到癌细胞有明显的能力适应和成为对靶向治疗耐药。联合两种或更多治疗应付不同癌-所致靶点可能有助于解决这个挑战，” “今天的批准提供一个新靶向治疗，当添加至威罗菲尼，证实在有BRAF突变-阳性黑色素瘤患者比单独威罗菲尼更大获益。”
Cotellic通过阻断一种已知酶的活性被称为MEK，是更大信号通路起作用。信号通路的异常活动可导致癌。Cotellic预防或减慢癌细胞生长。威罗菲尼，在美国以Zelboraf上市，是一个BRAF抑制剂影响相同通路的一个不同部分和在2011年被批准治疗已播散至机体其他部位或不能被手术去除的有黑色素瘤患者，其肿瘤表达一种基因突变被称为BRAF V600E，当被FDA批准非测试检测到。卫生保健提供者应在Cotellic与威罗菲尼联用开始治疗前用可得到的FDA批准的测试之一证实在他们的患者的肿瘤标本中存在BRAF V600 E或V600K突变。
在495例患者有以前未治疗过，BRAF V600突变-阳性晚期或不能被手术去除的黑色素瘤一项随机化临床研究证实Cotellic与威罗菲尼联用的安全性和疗效。所有研究参加者接受威罗菲尼和然后被随机化选择至还用或Cotellic或一种安慰剂。按平均，用Cotellic加威罗菲尼患者经历他们的疾病一个延长量的时间至恶化(开始治疗后约12.3个月)与之比较对只单独用威罗菲尼用参加者开始治疗后约7.2个月。此外，用Cotellic加威罗菲尼患者活的较长，在开始治疗后17个月约65%患者活着当只用威罗菲尼患者为半数。此外，用Cotellic加威罗菲尼70%患者他们的肿瘤经历完全或部分皱缩，与之比较用威罗菲尼加安慰剂患者中50%。
用Cotellic与威罗菲尼联用治疗最常见副作用是腹泻，对紫外线(UV)光敏感性(光敏反应)，恶心，发热和呕吐。
Cotellic可能致严重副作用包括对心肌损伤(心肌病)或对其他肌肉(横纹肌溶解综合证)，新皮肤肿瘤(原发性皮肤恶性病)，眼疾病(视网膜脱落)，严重皮疹，肝受损(肝毒性)，出血和严重皮疹由于对日光敏感性增加(光敏感)。用Cotellic人们应避免阳光暴露，穿保护性衣服，和一种宽广谱紫外线A/紫外线B防晒油对阳光烧伤保护。用Cotellic妇女应使用有效避孕，因为药物可致发育中胎儿危害。
Cotellic是在FDA的优先审评程序下审评该程序提供在治疗一种严重情况在安全性和有效性有潜力显著改善的药物申请递交时6个月的加急审评。Cotellic还接受孤儿药物指定，它提供奖励例如税收抵免，用户费用减免和资格对孤儿药物专有权有助和鼓励对罕见疾病药物的发展。
Cotellic和Zelboraf两药均有加州旧金山Genentech公司上市。
http://www.fda.gov/NewsEvents/Newsroom/PressAnnouncements/ucm471934.htm
Cotellic, cobimetinib (GDC-0973, RG7421) (formerly XL518)
Also known as: MEK inhibitor
Generic Name: cobimetinib
Date of Approval: November 10, 2015
Company: Genentech, Inc.
COTELLIC is indicated for the treatment of patients with unresectable or metastatic melanoma with a BRAF V600E or V600K mutation, in combination with ZELBORAF (vemurafenib).
Limitation of Use: COTELLIC is not indicated for treatment of patients with wild-type BRAF melanoma.
IMPORTANT SAFETY INFORMATION
Review the Full Prescribing Information for ZELBORAF for information on the serious risks of ZELBORAF.
WARNINGS AND PRECAUTIONS
The following can occur in patients treated with COTELLIC
New primary malignancies, including cutaneous and non-cutaneous malignancies
Hemorrhage, including major hemorrhages
Cardiomyopathy, defined as symptomatic and asymptomatic decline in left ventricular ejection fraction
Severe dermatologic reactions, including rash and other skin reactions
Serous retinopathy and retinal vein occlusion
Hepatotoxicity
Rhabdomyolysis
Severe photosensitivity
Embryo-fetal toxicity
Most Common Adverse Reactions
The most common (≥20%) adverse reactions with COTELLIC were diarrhea, photosensitivity reaction, nausea, pyrexia, and vomiting. The most common (≥5%) grade 3-4 laboratory abnormalities are increased GGT, increased CPK, hypophosphatemia, increased ALT, lymphopenia, increased AST, increased alkaline phosphatase, and hyponatremia.
New Drugs cobimetinib
Information
Generic Name: cobimetinib
Trade Name: Cotellic
Synonym: RG7421 (GDC-0973), Cotellic
Entry Type: New molecular entity
Development and Regulatory status
UK: Recommended for approval (Positive opinion)
EU: Recommended for approval (Positive opinion)
US: Approved (Licensed)
UK launch Plans: Available only to registered users
Actual UK launch date:
Comments
Nov 15: Approved in the US for use in combination with vemurafenib to treat advanced melanoma that has spread to other parts of the body or can’t be removed by surgery, and that has a BRAF V600E or V600K mutation [18].
11/11/2015 09:39:57
Sep 15: EU positive opinion for use in combination with vemurafenib for treatment of adults with unresectable or metastatic melanoma with a BRAF V600 mutation [16].
25/09/2015 12:35:42
Aug 15: Swissmedic, the Swiss licensing and supervisory authority of Switzerland, has approved cobimetinib, in combination with vemurafenib, as a treatment for patients with advanced melanoma. The regulatory submission was based on data from the PIII coBRIM trial. Roche filed a MAA with the EMA in late 2014 and a decision is anticipated before the end of 2015 [15].
28/08/2015 10:07:00
Jul 15: FDA extended its review of cobimetinib by 3 months to November 11, 2015 after Genentech submitted additional data from coBRIM, the PIII registrational trial of cobimetinib and vemurafenib in pts with BRAF V600 mutation-positive advanced melanoma [14].
02/07/2015 09:22:46
Feb 15: US FDA grants priority review status for cobimetinib, in combination with vemurafenib, for the treatment of BRAF, V600 mutation-positive advanced melanoma. This was based on results from the PIII coBRIM study [12].
20/02/2015 10:45:43
Dec 14: Filed in the US for treatment, in combination with vemurafenib, of people with BRAF V600 mutation-positive advanced melanoma. The filing is based on results of the coBRIM PIII study [11].
15/12/2014 12:02:50
Oct 14: Filed in the EU via the centralised procedure [10].
27/10/2014 13:55:08
Feb 14: Filing still planned for 2014. [3]
24/02/2014 11:05:16
Dec 12: Filings planned for 2014 [2].
05/03/2013 12:10:17
Trial or other data
Oct 15: Exelixis announces coBRIM met its secondary endpoint of demonstrating a statistically significant and clinically meaningful increase in overall survival for patients receiving the combination of cobimetinib and vemurafenib vs. vemurafenib monotherapy [17].
07/10/2015 11:34:08
Jun 15: Results from the coBRIM PIII study showed that the combination of cobimetinib and vemurafenib improved PFS (12.3 vs 7.2 months with vemurafenib alone) [13].
04/06/2015 11:20:11
Sep 14: PIII coBRIM published in NEJM. Median progression-free survival was 9.9 months in the combination group and 6.2 months in the control group (hazard ratio for death or disease progression, 0.51; 95% confidence interval [CI], 0.39 to 0.68; P<0.001). The rate of complete or partial response in the combination group was 68%, as compared with 45% in the control group (P<0.001), including rates of complete response of 10% in the combination group and 4% in the control group. Progression-free survival as assessed by independent review was similar to investigator-assessed progression-free survival. Interim analyses of overall survival showed 9-month survival rates of 81% (95% CI, 75 to 87) in the combination group and 73% (95% CI, 65 to 80) in the control group. Vemurafenib and cobimetinib was associated with a nonsignificantly higher incidence of adverse events of grade 3 or higher, as compared with vemurafenib and placebo (65% vs. 59%), and there was no significant difference in the rate of study-drug discontinuation. The number of secondary cutaneous cancers decreased with the combination therapy [12].
01/10/2014 14:42:46
Sep 14: Roche report new data for vemurafenib plus cobimetinib with a median progression-free survival rate of 9.9 months among advanced melanoma patients vs. 6.2 months for vemurafenib alone [8].
30/09/2014 10:53:29
Jul 14: Roche & Exelixis announce that cobimetinib in combination with vemurafenib met its primary outcome of prolonged PFS in the coBRIM study [7].
15/07/2014 07:03:48
Mar 14: Enrollment completed in coBRIM study [6].
23/06/2014 11:10:47
Feb 14: Results from coBRIM (NCT01689519) expected in 2014 [5].
06/03/2014 12:02:25
Jan 13: NCT01689519 a PIII multicentre, randomized, double-blind, placebo-controlled study comparing vemurafenib alone vs vemurafenib + GDC-0973 in 500 previously untreated BRAF V600 mutation-positive patients with unresectable locally advanced or metastatic melanoma (stage IIIc or stage IV). Vemurafenib 960mg will be given twice a day and GDC-0973 60mg once daily for days 1-21 of each cycle. Patients will receive treatment until disease progression, unacceptable toxicity or withdrawal of consent. The primary outcome is progression free survival. Patients started enrolling in Jan 13; the study is due to complete Apr 17 [1].
19/01/2013 17:28:18
Evidence Based Evaluations
NICE scope http://www.nice.org.uk/guidance/indevelopment/gid-tag523/documents
NIHR HSRIC http://www.hsc.nihr.ac.uk/topics/vemurafenib-and-cobimetinib-for-previously-untreat/
References
Available only to registered users
Category
BNF Category: Other immunomodulating drugs (08.02.04)
Pharmacology: Cobimetinib (GDC-0973) is a MEK inhibitor
Epidemiology: In England, in 2011, there were 11,121 new cases of malignant melanoma (representing 17.3 cases per 100,000 population). ~ 50% of melanomas harbour activating BRAF mutations and > 90% of these are BRAFV600 mutations [4]
Indication: Malignant melanoma
Additional Details: first-line in combination with vemurafenib
Method(s) of Administration
Oral
Company Information
Name: Roche
US Name: Roche
Further Information
Anticipated commissioning route (England) NHSE
High cost drug list? Awaiting Update
Tariff Chemotherapy is locally negotiated.
In NICE timetable: Yes
When: Jun / 2016
Note: www.nice.org.uk/guidance/indevelopment/gid-tag523
Implications Available only to registered users