A promising new drug candidate that may be effective against both actively dividing and slow-growing Mycobacterium tuberculosis (M. tb) has begun testing in humans, the National Institute of Allergy and Infectious Diseases (NIAID), part of the National Institutes of Health, announced this week.
The novel antibiotic, PA-824, may shorten the time needed to treat tuberculosis (TB), a contagious disease that claims approximately two million lives worldwide each year. In partnership with the non-profit New York-based Global Alliance for TB Drug Development (TB Alliance), NIAID contributed to the drug candidate’s preclinical safety and efficacy testing in animal models. Now, a clinical trial to assess PA-824’s safety, sponsored by the TB Alliance, has opened at a medical clinic in Lincoln, NE.
“The rapid movement of PA-824 through the development pipeline is a testament to the successful partnership between NIAID and the TB Alliance. It marks a significant milestone in progress toward our goal of making treatments for TB more effective and shorter in duration,” notes NIAID Director Anthony S. Fauci, M.D.
One-third of the global population — some two billion people — is infected with M. tb. A person may remain latently infected and harbor the bacteria, in a non-growing or slow-growing form, for decades with no symptoms. However, if the immune system is weakened by age, HIV or other infections, M. tb may be re-activated and the active form of the disease may emerge. Although most common in other countries where HIV prevalence is highest, approximately 14,000 cases of active TB are reported to the Centers for Disease Control and Prevention each year in the United States.
While TB is curable with antibiotics, the drug regimen is arduous and lengthy. The World Health Organization’s current recommendation for treatment of active TB includes the administration of up to 4 drugs for at least 6 months. PA-824 differs from most currently available TB drugs because it appears to attack M. tb in both the bacterium’s actively dividing and slow-growing stages. For this reason, researchers hope PA-824 will significantly reduce the time needed to cure TB.
In 2000, C. Kendall Stover, Ph.D., of Pathogenesis Corporation, and his co-authors, including NIAID scientist Clifton E. Barry, III, Ph.D., published the first evidence of PA-824’s potential TB-fighting abilities. In 2002, the TB Alliance acquired exclusive worldwide rights to PA-824 from the California-based biotechnology firm, Chiron Corporation.
NIAID provided support to the TB Alliance for continued development of PA-824 through the Institute’s Tuberculosis Antimicrobial Acquisition and Coordinating Facility (TAACF) (www.taacf.org). TAACF, established by NIAID in 1994, conducts prescreening and efficacy testing of potential anti-TB drugs at no cost to those who submit the compounds.
For PA-824 development, NIAID support included