The TB Alliance and its partners are leading the clinical development of a new generation of markedly improved TB cures. These drugs are the building blocks of novel TB regimens, which will speed the introduction and unleash the transformative impact of new, faster, and better TB drugs for drug-sensitive and drug-resistant TB.
The TB Alliance isn't just developing new TB drugs, but leading a revolution in the way that TB drugs are developed. The organization is using the regimen development paradigm to telescope the time it takes to develop novel, multi-drug treatments. Following a robust pre-clinical program and the establishment of the safety and efficacy of individual drug candidates, promising combinations of drugs are tested together to find the most impactful treatment.
CHANGING THE WAY
WE DEVELOP A NEW TB
Since the 1950s, researchers have known that TB treatment must be delivered in multi-drug regimens to prevent the development of drug resistance. Traditionally, when developing a new drug, researchers would replace an existing drug within the regimen or add the new candidate to the existing standard treatment. Each of these trials could last six years or longer, which means that a novel TB regimen could take decades to develop using this model. With more than 9 million new cases of TB each year and growing numbers of people resistant to the current treatment, this is an unacceptably long wait for those suffering.
The first novel TB drug regimen to begin development, PaMZ, consists of moxifloxacin, PA-824, and pyrazinamide. In a two- week Phase II trial, this regimen killed more bacteria than the current standard of care. The PaMZ regimen is currently being tested in an 8-week trial, in both TB and MDR-TB patients
The establishment and resulting efforts of the TB Alliance and the emergence of global philanthropy has lowered the obstacles to TB drug development. Over the last decade, there has been significant development of a global TB drug pipeline. With multiple compounds now in clinical development, there is now opportunity to test these new compounds together to find the best novel regimens or building blocks of novel regimens.
Given its global network of partners and not-for-profit designation, the TB Alliance is uniquely positioned to lead the field's regimen development efforts, and to find and test the most promising treatments together, regardless of sponsor. In 2010, the TB Alliance launched the first regimen clinical trial, whereby novel TB drug regimens — not single drugs — are the unit of development. Results of this trial validated this approach to TB research. Regimen-based development is integrated not only into the TB Alliance's clinical testing efforts, but into its preclinical research paradigm as well, to facilitate early identification of the building blocks and combinations of building blocks for tomorrow's TB regimens.