Developing biomarker assays to accelerate tuberculosis drug development: defining target product profiles

Area of Science:

• Biomarker assay development
• Clinical trial methodology
• Tuberculosis drug discovery

Background:

• Tuberculosis drug development faces challenges due to slow organism growth and difficulties in obtaining representative patient samples during treatment.
• Current methods for monitoring treatment efficacy in clinical trials have limitations, hindering the development of new anti-TB drugs.

Purpose of the Study:

• To establish target product profiles (TPPs) for biomarker assays to assess tuberculosis treatment response in early- and late-phase clinical trials.
• To define desirable performance and operational characteristics for biomarker assays used in tuberculosis drug development.

Main Methods:

• Consultation with subject-matter experts to define minimal and optimal criteria for biomarker assays.
• Development of TPPs encompassing scope, intended use, pricing, performance, and operational characteristics.
• Consideration of infrastructure and resource availability for clinical trial settings.

Main Results:

• Early-stage trial assays should quantify viable bacilli; late-stage assays should match bacterial load, predict relapse-free cure, and potentially replace culture conversion endpoints.
• Defined criteria for biomarker assays to guide development for phase 2 and 3 tuberculosis drug trials.
• Outlined TPPs aim to de-risk assay development and improve the definition of sterilizing activity for TB drugs.

Conclusions:

• Target product profiles provide a framework for developing effective biomarker assays to monitor tuberculosis treatment in clinical trials.
• These assays are crucial for evaluating drug efficacy, reducing treatment failure, and predicting relapse-free cure in tuberculosis patients.
• Implementing these TPPs will accelerate the development of novel tuberculosis therapeutics.