Preclinical TB Regimen Development
Mouse models are used to assess the activity of various TB drugs and regimens in acute, chronic, and disease-simulating “Kramnik” infections. The contributions of individual components of a regimen can be evaluated for impact on reducing bacterial lung burdens and duration of treatment required to achieve sterilization and relapse-free cure. Pharmacodynamic modeling of drug exposure and efficacy help direct the selection and development of optimized anti-TB drug regimens. Through this partnership with Johns Hopkins University, TB Alliance has evaluated more than 250 TB drug regimens.
M.tb, the bacterium that causes TB, is remarkably adept at developing resistance to drugs and therefore active TB must be fought with combination therapy. Today’s four-drug first-line TB treatment evolved through the addition and substitution of drugs into the existing regimen. Novel combinations offer the promise to transform treatment. However, modifying TB treatment one drug at a time is too lengthy, expensive, and inefficient a process. Today, the emerging gold standard in TB drug development is a regimen-based approach by which multiple new agents are combined early in the development process to create new TB drug regimens with the potential to shorten and simplify TB treatment. This approach also shows promise to develop regimens that could be effective against both TB and drug-resistant forms of TB.
This program continues to identify and rapidly advance the most promising combinations of potential new TB drugs to form future new regimens.This initiative seeks to promote regimen-based development by qualifying new preclinical models with better predictability for human disease. These new models could contribute to identifying optimized drug combinations and earlier registration and approval of new, improved, and safe TB drug regimens.