ABSTRACT

Introduction

Tuberculosis is an infectious disease that affected more than 50 million people and killed 6.7 million patients in the past 5 years alone. Additionally, rising incidence of treatment resistance threatens the global effort to eradicate this disease. With limited options available, additional novel antibiotics are needed for the treatment of multidrug-resistant tuberculosis (MDR-TB). Telacebec is a first-in-class antibiotic that targets the pathogen’s energy metabolism.

Areas covered

This paper provides an overview of the recent progress in the development and testing of telacebec. We discuss published clinical data and examine the design and setup of its clinical trials. We also offer insights on the therapeutic potential of telacebec and aspects of which should be evaluated in the future.

Expert opinion

The first phase 2a trial showed a correlation between dosage and bacterial load in patient sputum, which should be confirmed using a direct measurement method such as colony-forming unit counting. Its clinical efficacy, favorable pharmacokinetic properties, low arrhythmogenic risk, and activity against MDR-TB strains make telacebec a suitable candidate for further development. Future clinical testing in combination with approved second-line drugs will reveal its full potential against MDR-TB. Considering recent preclinical studies, we also recommend initiating clinical trials for Buruli ulcer and leprosy.

中文翻译：

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Telacebec：一种用于治疗结核病 (TB) 的研究性抗菌药物

摘要

介绍

结核病是一种传染病，仅在过去 5 年就影响了超过 5000 万人，并导致 670 万患者死亡。此外，治疗耐药性发病率的上升威胁着全球根除这种疾病的努力。由于可用的选择有限，需要额外的新型抗生素来治疗耐多药结核病 (MDR-TB)。Telacebec 是一种针对病原体能量代谢的一流抗生素。

涵盖的领域

本文概述了 telacebec 的开发和测试的最新进展。我们讨论已发表的临床数据并检查其临床试验的设计和设置。我们还提供了有关 telacebec 的治疗潜力以及未来应评估的方面的见解。

专家意见

第一阶段 2a 试验显示剂量与患者痰液中细菌负荷之间的相关性，应使用直接测量方法（如菌落形成单位计数）来确认。其临床疗效、良好的药代动力学特性、低致心律失常风险和对 MDR-TB 菌株的活性使 telacebec 成为进一步开发的合适候选者。未来与批准的二线药物联合的临床试验将揭示其对抗 MDR-TB 的全部潜力。考虑到最近的临床前研究，我们还建议启动布鲁里溃疡和麻风病的临床试验。