近日，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。
SIRTURO® Is the First Medication for Pulmonary MDR-TB With a Novel Mechanism of Action in Over 40 Years
INDICATIONS AND USAGE
SIRTURO® (bedaquiline) is a diarylquinoline antimycobacterial drug indicated as part of combination therapy in the treatment of adults (≥18 years) with pulmonary multi drug resistant tuberculosis (MDR TB). Reserve SIRTURO® for use when an effective treatment regimen cannot otherwise be provided. Administer SIRTURO® by directly observed therapy (DOT).
This indication is approved under accelerated approval based on time to sputum culture conversion. Continued approval for this indication may be contingent upon verification and description of clinical benefit in confirmatory trials.
Limitations of Use
Do not use SIRTURO® for the treatment of:
•Latent infection due to Mycobacterium tuberculosis
•Drug-sensitive tuberculosis
•Extrapulmonary tuberculosis
•Infections caused by non-tuberculous mycobacteria
The safety and efficacy of SIRTURO® in the treatment of HIV-infected patients with MDR-TB have not been established as clinical data are limited.
Mechanism of Action
•SIRTURO® is the first anti-TB drug to interfere with bacterial energy metabolism.
•SIRTURO® specifically inhibits mycobacterial ATP (adenosine 5'-triphosphate) synthase, by binding to subunit c of the enzyme that is essential for the generation of energy in Mycobacterium tuberculosis.
Download a comprehensive resource on SIRTURO® (bedaquiline) tablets
..IMPORTANT SAFETY INFORMATION
WARNINGS: INCREASED MORTALITY; QT PROLONGATION
Increased Mortality
•An increased risk of death was seen in the SIRTURO® treatment group (9/79, 11.4%) compared to the placebo treatment group (2/81, 2.5%) in one placebo-controlled trial. Only use SIRTURO® when an effective treatment regimen cannot otherwise be provided.
QT Prolongation
•QT prolongation can occur with SIRTURO®. Use with drugs that prolong the QT interval may cause additive QT prolongation. Monitor ECGs. Discontinue SIRTURO® if significant ventricular arrhythmia or if QTcF interval prolongation of greater than 500 ms develops.
Warnings and Precautions
Increased Mortality
An increased risk of death was seen in the SIRTURO® treatment group. The imbalance in deaths is unexplained. No discernible pattern between death and sputum culture conversion, relapse, sensitivity to other drugs used to treat tuberculosis, H