LEAP TB: Update from the LEAP Working Group on Development
of Long-Acting Approaches to the Treatment of Tuberculosis
Speaker: Susan Swindells, Professor of Infectious Diseases at University of Nebraska Medical Center
Provided an update from the LEAP TB Working Group, including priority targets and approaches to developing LA formulations for TB prevention and treatment.
Length of standard TB treatment and characteristics of existing TB agents pose major challenges for the development of LA TB formulations.
Standard TB treatment comprises a 6-month regimen of TB drugs, which are dissimilar to successful LA formulations developed for other diseases (i.e. half-life, target concentration, water solubility, daily oral dose and lipophilicity).
LTBI treatment will be the first LA target.
The global LTBI burden is enormous, LTBI treatment completion rates are sub-optimal, and LA LTBI treatment is potentially achievable, as regimens are shorter (1 or 3 months vs 6 months) and incorporate fewer drugs (1-2 drugs vs 4 drugs) than standard treatment for active TB.
Approach towards LAI 1HP-RPT (1-month of isoniazid plus rifapentine) includes development of a novel isoniazid prodrug.
Newer TB drugs developed for drug-resistant TB have more promising profiles for LA treatment. Optimal dosing of LA rifapentine will be determined using a mouse model (Nuermberger-Ammerman laboratory at JHU). A novel isoniazid prodrug is under development to achieve lower water solubility than the current formulation (Caren Myers, Department of Pharmacology and Molecular Sciences at JHU).
The LONGEVITY program research consortium will facilitate development of LA TB prevention.
The program aims to repurpose key medicines as LAI formulations for malaria prevention, tuberculosis prevention, and HCV cure and includes infrastructure for sustainable translational capacity and a roadmap to market. The research consortium comprises Johns Hopkins University, University of Nebraska Medical Center, University of Liverpool, Clinton Health Access Initiative, Medicines Patent Pool, Treatment Action Group, and Tandem Nano, LTD.