New Tuberculosis Drug Cocktail Shows Promise

A novel drug cocktail eliminates 99% of Mycobacterium tuberculosis, the causative agent of tuberculosis (TB), according to a new phase II study.

Researchers at Stellenbosch University (Cape Town, South Africa) conducted a prospective, randomized, early bactericidal activity (EBA) study involving treatment-naive, drug-susceptible patients with uncomplicated pulmonary TB who were admitted to hospitals in Cape Town (South Africa). The patients were randomized to receive bedaquiline, bedaquiline-pyrazinamide, PA-824-pyrazinamide, bedaquiline-PA-824, PA-824-moxifloxacin-pyrazinamide (PaMZ), or unmasked standard anti-TB treatment as positive control. The primary outcome was the 14-day EBA assessed in a central laboratory from the daily fall in colony forming units (CFU) of M. tuberculosis per mL of sputum in daily overnight sputum collections.

The results showed that the mean 14-day EBA of PaMZ was significantly higher than that of bedaquiline, bedaquiline-pyrazinamide, bedaquiline-PA-824, but not PA-824-pyrazinamide, and comparable with that of standard treatment. Treatments were well tolerated and appeared safe. An ongoing Phase IIb trial to study the PaMZ drug cocktail is being conducted in a larger population over a two-month treatment regimen in South Africa, Brazil, and Tanzania. The study was published on September 15, 2012, in the Lancet.

“Treating drug-sensitive and drug-resistant TB with the same regimen can simplify the delivery of TB treatment worldwide,” said lead author Andreas Diacon, MD. “The results of this study give healthcare providers on the front lines of the TB epidemic hope for better, faster tools needed to stop this disease.”

The new combination therapy consists of the novel TB drug candidate, PA-824; moxifloxacin--an established antibiotic not yet approved for use in first-line TB therapy; and pyrazinamide, an existing TB drug. The ability of the three drug cocktail to eliminate 99% of the bacteria in only two weeks provides a stark contrast to the six-month treatment regimen of TB therapies that is currently on the market, and would not only decrease treatment costs but also increase compliance of patients prescribed current TB-related therapy, which has resulted in the emergence of drug-resistant TB strains, including multidrug-resistant TB (MDR-TB) and extensively drug-resistant TB (XDR-TB).

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