强生旗下Sirturo在欧洲获得批准，成为几十年来进入欧洲市场的新类型结核病(TB)治疗药物之一。欧盟已授予Sirturo (bedaquiline)上市许可，做为肺多重耐药(MDR) TB合并治疗方案的一部分，该病症属孤儿适应症，在欧洲影响大约万分之二的人口。
这次的批准基于一项2期临床试验，强生下属子公司杨森制药正在开展一项3期临床试验，以确证这款药物的风险和收益。Sirturo于2012年年底在美国获得批准，它是TB治疗的一项重要科学进展，因为这款药物是首款抑制分枝杆菌三磷酸腺苷合酶的药物，分枝杆菌三磷酸腺苷合酶是结核菌能量产生所必需的一种酶。
对强生来说，这款药物销售未有很大的预期，因这它用于不能耐受其它药物或感染了耐药菌株的患者，但据分析师们的预测，这款药物全球年销售峰值可能会达到约3亿美元。然而，从公共健康的角度来看，这款药物的重要性怎么强调都不过分，尽管其标签中需要添加一项罕见心血管副作用(QT间期延长)的警告。
“MDR-TB与高死亡率相关，对公共健康造成明显威胁，作为感染了耐药菌株的个人，通常不能获得充分的治疗，并将他们的感染进行传播，”阿姆斯特丹大学热带医学和旅行医学中心主管Martin Grobusch教授评论说。Bedaquiline的批准“是应对这种快速增长疾病迈出的关键一步，加快了患者获取急需的治疗药物，”他补充说。
治疗多药耐药结核病完全新颖的药物一直寥寥无几，去年欧洲批准了一连串的新药，有日本大冢的Deltyba (delamanid)，这款药物去年9月获得有条件批准，另外还有Pharma SA的对氨水杨酸。近年来，TB对至少包括异烟肼和利福平在内的一线治疗药物耐药的负担因缺乏新的治疗选择而迅速增长，异烟肼和利福平是两款重要的抗结核病治疗药物。
New Drugs Online Report for bedaquiline
Information
Generic Name: bedaquiline  
Trade Name: Sirturo 
Synonym: TMC 207 
Entry Type: New molecular entity  
Development and Regulatory status
UK: Launched 
EU: Launched 
US: Approved (Licensed) 
UK launch Plans: Available only to registered users
Actual UK launch date: June 2014 
Comments
Jun 14: Launched in the UK [10].
09/06/2014 15:51:37 
Mar 14: Approved in the EU [9].
13/03/2014 09:19:53 
Dec 13: EU CHMP recommends granting conditional approval of bedaquiline for use as part of an appropriate combination regimen for pulmonary multidrug-resistant TB in adults when an effective treatment regimen cannot otherwise be composed for reasons of resistance or tolerability [8].
23/12/2013 08:40:43 
Dec 12: Approved in the US as part of combination therapy to treat adults with multi-drug resistant pulmonary TB when other alternatives are not available [7].
02/01/2013 15:47:41 
Nov 12: an FDA advisory committee voted 18-0 in favour of efficacy of bedaquiline, for combating multidrug-resistant pulmonary TB, but voted 11-7 in support of safety data; concerns about the effects of the treatment on the liver and heart have been raised [6]. 
29/11/2012 22:27:07 
Sep 12: Granted priority review in the US [5].
11/09/2012 17:00:52 
Aug 12: Marketing Authorisation Application submitted to the European Medicines Agency seeking conditional approval for the use of bedaquiline (TMC207) as an oral treatment, to be used as part of combination therapy for pulmonary, multi-drug resistant tuberculosis (MDR-TB) in adults. [4] 
03/09/2012 08:29:11 
July 12: New Drug Application submitted to the US FDA seeking accelerated approval for the use of the bedaquiline as an oral treatment, to be used as part of combination therapy for pulmonary, multi-drug resistant tuberculosis (MDR-TB) in adults. If approved by the FDA, bedaquiline would be the first drug with a new mechanism of action for TB in more than 40 years and the first and only one specifically indicated for MDR-TB. [1]
05/07/2012 16:53:58 
Trial or other data
Aug 15: NHS England has published a new Clinical Commissioning Policy making Sirturo( and Otsuka’s Deltyba) routinely available on the NHS for treatment of pulmonary multi-drug resistant TB in adults, when an effective treatment regimen cannot otherwise be composed for reasons of resistance or tolerability [11].
26/08/2015 11:11:28
July 12: Phase III trial TMC207-C210 a double-blind study comparing nine months of treatment with bedaquiline versus placebo (both with a background regimen) is planned to start recruiting in Q4 2012. This study will evaluate a new regimen of seven drugs for a shorter treatment duration (nine months of treatment) than the current 18 to 24 months WHO standard of care. [1] 
05/07/2012 16:59:17
July 12: Two Phase II studies in patients with MDR-TB. (1) TMC207-C208 was conducted in two independent stages: stage 1 was a controlled, randomised, exploratory trial and stage 2 was a controlled, randomised superiority trial in MDR-TB patients. 161 patients received treatment for 24 weeks followed by continuation of the background therapy for an additional 12 to 18 months. (2) TMC207-C209 was an open-label trial in MDR-TB patients, in which bedaquiline was administered as 400 mg once daily for two weeks followed by 200 mg three times weekly for 22 weeks in combination with an individualised background regimen for MDR-TB, followed by continued administration of the background regimen for 12 to 18 months (n=233). [1]
05/07/2012 16:58:52

Evidence Based Evaluations
AWMSG  http://www.awmsg.org/awmsgonline/app/appraisalinfo/1334 
EPAR  
FDA doc  http://www.fda.gov/downloads/AdvisoryCommittees/CommitteesMe

etingMaterials/Drugs/
Anti-InfectiveDrugsAdvisoryCommittee/UCM329258.pdf 
References  
Available only to registered users
 Category
BNF Category: Antituberculous drugs (05.01.09)
Pharmacology: diarylquinolone compound that inhibits ATP synthase (ATPase) in Mycobacterium tuberculosis  
Epidemiology: According to the Health Protection Agency’s annual TB report, the number of drug resistant cases of TB (when a patient fails to respond to 1 of the 4 main antibiotics used to treat the infection) continue to rise, with 431 reports in 2011, up from 342 in 2010 – an increase of 26%. Overall, 8963 new cases of TB were reported to the Agency in 2011, up from 8410 cases in 2010. [3]  
Indication: Tuberculosis 
Additional Details: multi-drug resistant 
Method(s) of Administration  
Oral 
Company Information
Name: Janssen-Cilag 
US Name: Johnson & Johnson 
Further Information
Anticipated commissioning route (England) - 
High cost drug list? Yes
Implications Available only to registered users
【药品名称】SIRTUROTM
【药品通用名】SIRTUROTM
【规格】100 mg片
【不良反应】（1）报道的最常见不良反应在≥10%用SIRTURO治疗患者是恶心，关节痛，和头痛。
（2）在≥10%用SIRTURO治疗患者报道的另外不良事件和频率较高于安慰剂治疗组是咯血和胸痛。
【适应症和用途】SIRTURO是一种diarylquinoline抗分枝杆菌药适用于作为有肺多药耐药性结核(MDR-TB)成年(≥18岁)联合治疗的一部分，当一个有效的治疗方案不能以其他方式提供贮备SIRTURO使用。SIRTURO不适用为治疗潜伏，肺外或药物敏感结核。
【用法用量】与食物400 mg每天1次共2周接着200 mg每周3次共22周。与水整吞服SIRTURO片。
【警告和注意事项】 （1）用SIRTURO可能发生QT延长。经常监视ECG。
（2）如发生显著室性心律失常或QTcF间期> 500 ms终止SIRTURO。
（3）使用延长QT间期药物可致另外QT延长。更频繁监视ECG。
（4）使用SIRTURO曾报道肝相关不良药物反应。监视肝相关实验室检验。
（5）不遵守的治疗方案可能导致失败或耐药性。
【禁忌症】无
【生产企业】Janssen Therapeutics