PA-824, the first TB Alliance compound, acquired through an exclusive license deal with Chiron Corporation in June 2002, has moved briskly through the R&D pipeline, passing several important milestones in preclinical development. Key issues of compound synthesis, toxicology and preclinical efficacy have been addressed.
Early research during the discovery stage showed that PA-824 and its analogs - members of a family of a class of drugs called nitroimidazopyrans, or NAPs - demonstrated activity against both drug-sensitive and multi-drug resistant strains of TB, signaling possible improvements in TB treatment.
In the preclinical stage, results so far have been promising. Studies have demonstrated the feasibility of PA-824 synthesis at the larger scale required for animal and clinical trials. In extensive testing, PA-824 exhibited no evidence of genotoxicity, nor evidence of interacting with other normal cell functions.
With support provided by the National Institute of Allergy and Infectious Diseases (NIAID), part of the National Institute of Health (NIH), Doris Rouse, Ph.D., director of Global Health at the Research Triangle Institute, is the project manager of the Development Team, which includes Drs. Barbara Laughon, Christopher Lipinski, Clifton Barry, Christine Sizemore and Ken Stover of the Scientific Advisory Committee.
Dr. Rouse said, “We are excited about the progress of PA-824. With each milestone it passes, we gain increased confidence in the promise of this class of compounds for improving TB treatment. Now we want to move it as quickly as possible through the next phase of animal studies.”
Ongoing development tasks include additional animal studies to assess the safety and efficacy of PA-824. Further, the TB Alliance is working to optimize the synthesis of PA-824 to reduce production costs. If extensive animal toxicology studies in the next year are successful, the TB Alliance plans to enter Phase I clinical trials.
To ensure further development of this most promising class of drug candidate, the TB Alliance is also pursuing research into analogs of PA-824.