The bacterium that causes TB is remarkably adept at developing resistance to drugs, therefore active TB must be fought with combination therapy. Today’s four-drug first-line TB treatment, which is old and highly inadequate to tackle today’s epidemic, evolved through the addition and substitution of drugs into an existing regimen. To bring a single TB drug through clinical trials takes a minimum of six years, thus the development of a fully novel treatment regimen could take decades. With nearly 2 million people dying from TB yearly, this is absolutely too long to wait.
However, with a substantial global TB drug portfolio and the backing of the Critical Path to TB Drug Regimens partners, the TB Alliance has introduced a paradigmatic shift in the way TB drug development is conducted. Instead of developing single drugs, one at a time, entire new regimens of drugs are currently being tested together.
Regimen-based development has the potential to save decades of development time, millions of dollars, and precious lives. In 2010, the TB Alliance launched the first-ever TB drug trial testing multiple new compounds in combination, NC-001. The novel regimen it tested - PA-824, moxifloxacin, and pyrazinamide - performed extremely well as compared to the standard of care, showing the potential for a single regimen to treat both drug-sensitive TB and MDR-TB in four to six months. This regimen also performed well in the NC-002 trial, which tested PaMZ for two months in patients with TB and MDR-TB. This regimen is now poised to enter a Phase 3 global registration trial known as STAND. A simpler, safer, and faster TB cure would enable the global scale-up, particularly of treatment for MDR-TB.
The TB Alliance also received a grant from the United States Food and Drug Administration to support an initiative, in partnership with Johns Hopkins University, to expand a pre-existing program devoted to testing TB drugs in combination early in the drug development process to identify and advance novel treatment 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.