TEBULA

The challenge

In addition to tuberculosis, mycobacteria cause other diseases that have a significant impact in sub-Saharan Africa, including leprosy (caused by M. leprae) and Buruli ulcer (caused by M. ulcerans). Although not as common or deadly as TB, leprosy and Buruli ulcer still have a major impact in many parts of sub-Saharan Africa. Both are associated with long-lasting and disfiguring skin lesions, leading to discrimination, social stigma, and reduced quality of life and economic opportunities. 

Mycobacteria are hardy bacteria and difficult to kill, so drug treatments tend to be long and complex. Although effective, current treatments for leprosy require patients to take a cocktail of different drugs for up to 12 months, while Buruli ulcer treatment is based on a course of three pills taken at different times of the day for 2 months. Treatments also have side effects, including skin discolouration, which can exacerbate stigmatisation. 

Recently, a new drug has been discovered, telacebec, that is highly active against mycobacterial infections. The drug inhibits energy-generating biochemical pathways in mycobacteria. Both M. leprae and M. ulcerans are highly sensitive to telacebec, as genome shrinkage during their evolution has led to the loss of genes encoding alternative energy-generating systems.

The project

The TEBULA project is exploring whether telacebec is also effective for leprosy and Buruli ulcer, building on research into its use as a possible treatment for tuberculosis.

Phase I and II studies have already shown that telacebec is safe. A phase II trial of telacebec for Buruli ulcer has started in Australia, and results from this study will inform activities of the TEBULA project in sub-Saharan Africa.

The primary aim of the project is to evaluate shorter, simpler treatments for the two conditions. This would make it easier for patients to adhere to treatment regimens and reduce the pressure on health systems. For Buruli ulcer, a clinical trial in Benin, Côte d’Ivoire, and Ghana will compare the time required for lesions to heal when patients receive a shortened 4-week course of telacebec versus standard 2-month antibiotic treatment. The study will also explore patient perspectives on treatment and its impact and will have a practical focus, examining factors that may influence the introduction of telacebec into routine care.

For leprosy, the team is organising a phase II study to identify the optimal dose of telacebec to include in multi-drug treatment regimens. This study, in Benin, Côte d’Ivoire and Ethiopia, will compare different doses of telacebec as well as daily and monthly dosing – the latter is anticipated to be effective and would greatly simplify treatments. Because current treatment is highly effective, telacebec is not expected to improve clinical outcomes. The trial is therefore assessing multiple clinical, patient-related and health systems issues to identify the potential benefits of telacebec use.

Impact

The TEBULA project will accelerate the development of a potentially transformative drug for two neglected skin conditions. It will:

• Show whether telacebec is clinically effective against Buruli ulcer and leprosy.
• Reveal whether simplified treatment regimens can be introduced.
• Indicate whether patients experience improved quality of life with telacebec-based treatments.

By simplifying and shortening treatment for Buruli ulcer and leprosy, telacebec could reduce pill burden and treatment duration, improve treatment adherence, accelerate recovery, minimise the risks of stigmatisation and mental health impacts, and reduce demands on health systems.