The Food and Drug Administration (FDA) has approved pretomanid tablets (TB Alliance) in combination with bedaquiline and linezolid for the treatment of adults with pulmonary extensively drug resistant (XDR), treatment-intolerant or nonresponsive multidrug-resistant (MDR) tuberculosis (TB).
Pretomanid is an oral nitroimidazooxazine antimycobacterial that works by killing actively replicating M. tuberculosis by inhibiting mycolic acid biosynthesis, thereby blocking cell wall production. It was approved under the Limited Population Pathway for Antibacterial and Antifungal Drugs, or LPAD pathway.
The approval was based on the 6-month, open-label, phase 3, Nix-TB trial that evaluated the safety and efficacy of pretomanid in combination with bedaquiline and linezolid in patients (N=109) with extensively drug-resistant TB (XDR-TB) or multidrug-resistant TB (MDR-TB) who were treatment-intolerant or nonresponsive. Patients received a combination regimen of pretomanid, bedaquiline, and linezolid for 6 months (extended to 9 months in 2 patients) with 24 months of follow-up.
Results showed that 95 out of 107 patients successfully achieved a negative culture after 6 months of treatment and an additional 6 months of post-treatment follow-up. Outcomes were similar for both HIV negative and HIV positive patients.
With regard to safety, the most common treatment-emergent adverse events were peripheral neuropathy, acne, anemia, nausea, vomiting, headache, increased liver enzymes, dyspepsia, decreased appetite, rash, pruritus, abdominal pain, pleuritic pain, lower RTI, hyperamylasemia, visual impairment, back pain, cough, hypoglycemia, and diarrhea.
“Until very recently, people infected with highly drug-resistant TB had poor treatment options and a poor prognosis,” said Dr Francesca Conradie, principal investigator of the Nix-TB trial. “This new regimen provides hope with 9 out of 10 patients achieving culture negative status at 6 months post-treatment with this short, all-oral regimen.”
TB Alliance is a non-profit organization that focuses on developing affordable drug regimens for TB. Pretomanid is expected to be available in the US by the end of this year.
For more information visit tballiance.org.