Pretomanid is a new oral anti-tuberculosis drug developed with assistance from NIAID.
On August 14, 2019, the U.S. Food and Drug Administration (FDA) approved a new anti-tuberculosis (TB) drug, pretomanid (PA-824). Pretomanid is only the third anti-TB drug approved by the FDA in the past 40 years and is approved for use in combination with bedaquiline and linezolid for people with the most serious TB infections, extremely drug-resistant TB (XDR-TB) and treatment-intolerant/non-responsive multidrug-resistant (MDR-TB) TB. Pretomanid was originally discovered in 2000 by the Pathogenesis Corporation in collaboration with NIAID's Division of Intramural Research (DIR). It was developed by the TB Alliance, which was formed as a non-profit development partnership positioned to leverage a global network of public and private partners. NIAID's DIR elucidated the mechanism of action, evaluated pretomanid in an animal model and tested it in combination with other drugs to assess safety. NIAID's Division of Microbiology and Infectious Diseases (DMID) and Division of AIDS (DAIDS) conducted multiple preclinical animal and safety/toxicology studies on the drug, both alone and in combination with other compounds. DMID contributed project management support and conducted clinical studies to advance pretomanid's development. Pretomanid was approved in 2019 by the FDA under the Limited Population Pathway for Antibacterial and Antifungal Drugs based promising clinical data from the TB Alliance's NixTB Phase 3 trial in South Africa.
Pretomanid is part of the World Health Organization (WHO)'s recommended treatment for drug-resistant tuberculosis (DR-TB). This prequalification assures the safety, quality, and efficacy of the drug.
The WHO recommends a 6-month combination treatment regimen that includes pretomanid, bedaquiline, linezolid, and moxifloxacin (BPaLM). The BPaLM regimen is the preferred treatment for eligible patients with DR-TB. The CDC has issued Provisional Guidance for the Use of Pretomanid as part of a Regimen [Bedaquiline, Pretomanid, and Linezolid (BPaL)] to Treat Drug-Resistant Tuberculosis Disease in the United States.
NIAID's support was critical in helping advance this important new drug to licensure and adoption by international tuberculosis control programs.