BOSTON — A combination treatment consisting of bedaquiline, pyrazinamide and PA-824 demonstrated early bactericidal activity against tuberculosis and will be studied in future, longer duration trials, researchers reported here at the 2014 Conference on Retroviruses and Opportunistic Infections.
“There were two main findings in this study,” Andreas Diacon, MD, professor at Stellenbosch University in Cape Town, South Africa, said during the presentation. “The first is that this combination treatment looks as good as our current standard treatment. The surprising finding is that clofazimine, which is currently used as a second-line treatment for multidrug-resistant TB, demonstrated no bactericidal activity, either alone or in combination with other agents.”
In the prospective, randomized, open-label trial, patients with smear-positive TB were randomly assigned to seven treatment groups. Patients in each group were assigned to various single or combination treatments that included isoniazid, rifampicin, pyrazinamide, ethambutol, clofazimine (Lamprene, Novartis), bedaquiline (Sirturo, Janssen) or PA-824, an investigational agent. The primary endpoint was early bactericidal activity, measured by the change in log colony-forming units (CFU) per milliliter of sputum for 14 days.
The seven treatment groups each included 15 patients. The standard regimen, which includes isoniazid, rifampicin, pyrazinamide and ethambutol, had bactericidal activity similar to prior studies. The combination of PA-824, bedaquiline and pyrazinamide had bactericidal activity that was comparable to the standard regimen. Clofazimine did not have any early bactericidal activity and it did not add to the activity of the studied combinations.
Diacon said testing TB combinations in a traditional way, by developing a new drug and taking it to marketing, and then testing it in combination regimens would take about 20 years to complete. The TB Alliance is working to shorten this time by developing new drugs and testing combinations with old drugs early to develop new regimens. Drugs that look promising in the laboratory and mouse models are tested in humans for 2 weeks to determine whether they are safe, tolerable and efficacious.
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Diacon A. #97LB. Presented at: CROI 2014; March 3-6, 2014; Boston.
Disclosure: Diacon reports no relevant financial disclosures.