Telacebec: an investigational antibacterial for the treatment of tuberculosis (TB)

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.

KEYWORDS:

• Cytochrome bcc:aa₃
• Mycobacterium tuberculosis
• oxidative phosphorylation
• Q203
• respiration

Article highlights

• Telacebec is a first-in-class antibiotic that inhibits growth of M. tuberculosis by targeting its energy metabolism. The compound has undergone three clinical studies, the latest being a phase 2a efficacy trial

• Telacebec was established as a safe oral drug in single as well as multiple dosing, with no reported arrhythmogenic alerts

• Preliminary result of the phase 2a study revealed a positive relationship between sputum bacterial load and drug dosage

• Telacebec is suitable for further development where the effect of longer treatments as well as its combination with other antitubercular drugs should be explored, especially against drug-resistant tuberculosis

Declaration of interest

The authors have no relevant affiliations or financial involvement with any organization or entity with a financial interest in or financial conflict with the subject matter or materials discussed in the manuscript. This includes employment, consultancies, honoraria, stock ownership or options, expert testimony, grants or patents received or pending, or royalties.

Disclosure statement

Peer reviewers on this manuscript have no relevant financial or other relationships to disclose.

Additional information

Funding

This work was supported by the National Research Foundation (NRF) Singapore under its Investigatorship Program (grant NRF-NRFI06-2020-0004) and NRF Competitive Research Programme (Project Award Number NRF-CRP18-2017-01).