MELBOURNE, Australia — A once-daily oral regimen known as PaMZ shows promise in both drug-sensitive and multidrug-resistant tuberculosis (TB), new research shows.
After 8 weeks of treatment, more patients treated with PaMZ than with the standard TB protocol were culture-negative (71% vs 38%), said Dan Everitt, MD, senior medical officer at the Global Alliance for TB Drug Development.
This could be "a paradigm change for shortening and simplifying drug therapy for drug-sensitive and drug-resistant TB," he said. Drug-resistant patients typically require 5 to 7 drugs given over a 2-year period, with daily injections administered in the first 6 months.
Dr. Everitt presented the study results here at the 20th International AIDS Conference.
The study was conducted at 8 sites in South Africa and Tanzania. The primary end point was the rate of change in colony-forming units from sputum on solid culture over an 8-week period.
About 20% of the 181 study participants was coinfected with HIV.
Drug-sensitive patients were randomized to 1 of 2 PaMZ regimens or the standard TB protocol, consisting of isoniazid, rifampicin, pyrazinamide, and ethambutol.
The PaMZ regimen consisted of moxifloxacin 400 mg and pyrazinamide 1500 mg, plus PA-824 100 mg or PA-824 200 mg.
All drug-resistant patients received the 200 mg PaMZ regimen.
Investigators found that the PaMZ regimen has active bactericidal activity.
Table. Daily Reductions in Colony-Forming Units
|Treatment Groups||Reduction Per Day|
|200 mg PaMZ regimen||0.155|
|100 mg PaMZ regimen||0.133|
|Standard TB protocol||0.112|
|200 mg PaMZ regimen||0.117|
Median time to the first negative culture was significantly shorter with the 200 mg PaMZ regimen than with the standard TB protocol (28 vs 35 days).
The percentage of grade 3 and 4 adverse events was similar in all treatment groups.
"Going to a 4-month regimen for drug-sensitive patients cuts the amount of time on therapy by 30%," Dr. Everitt said. It is hoped that "more patients will comply with the regimen and we'll have less drug resistance developing as a result."
This regimen could change TB therapy, said Mel Spigelman, MD, who is CEO and president of the Global Alliance for TB Drug Development.
An estimated 2 billion people are infected with TB, and about 1.3 million of these die every year.
TB is now also the leading killer of patients with HIV. Drugs can interact with some antiretroviral treatments, so patients with HIV can be problematic.
Currently, TB drugs can cost thousands of dollars per treatment course, which is "clearly not doable in poor countries," where TB dominates, Dr. Spigelman pointed out.
His organization operates as a not-for-profit product-development partnership that can produce new drugs for considerably less than typical pharmaceutical companies. For example, the cost of a regimen like PaMZ will be about 90% less than it costs today.
However, that does not take into account costs to the healthcare system, which are even greater in terms of their burden on society," he explained.
The Alliance is now poised to launch the Shortening Treatment by Advancing Novel Drugs (STAND) trial, a phase 3 study of PaMZ in 1500 patients.
Theoretically, shortening treatment duration and targeting drug-sensitive and drug-resistant TB with the same regimen should simplify treatment, said Haileyesus Getahun, MD, from the World Health Organization Global TB Programme in Geneva.
"The next phase of the trial is to consolidate these findings with careful evaluation of the implications of background resistance of existing drugs," he told Medscape Medical News.
Dr. Getahun said he agrees that "the quest for novel TB drugs and shorter treatment regimens has to be intensified and expedited if we are ever to make a dent in this global epidemic that kills 1.3 million people every year."
The Global Alliance for TB Drug Development is supported by multiple donors, including the Bill & Melinda Gates Foundation, the National Institute of Allergy and Infectious Diseases, and the European Commission. Dr. Everitt, Dr. Spigelman, and Dr. Getahun have disclosed no relevant financial relationships.
20th International AIDS Conference: Abstract MOAB0202. Presented July 21, 2014.
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Cite this: New Tuberculosis Regimen Works Faster, Costs Less - Medscape - Jul 29, 2014.