Activity in treatment-naive patients

Thursday, October 09th, 2008 by hinrich

Response in tuberculosis patients

First results from early bactericidal activity studies with TMC207/R207910 are being published. Rustomjee et al. have just published their article "Early Bactericidal Activity and Pharmacokinetics of the Diarylquinoline TMC207 in Treatment of Pulmonary Tuberculosis" in the journal Antimicrobial Agents and Chemotherapy.

The main findings of this phase IIa study with respect to TMC207/R207910 are the following: 75 treatment-naive patients with smear-positive pulmonary tuberculosis were given one of five different oral treatments. Three different concentrations of TMC207/R207910 (25 mg, 100 mg, and 400 mg), rifampin (600 mg), or isoniazid (300 mg) were given daily for 7 days. Sputum was collected daily and plated on selective agar plates to investigate how many Mycobacterium tuberculosis colonies still form. The researchers demonstrated significant bactericidal activity with the highest dose of TMC207/R207910 (400 mg) from day 4 onward. The effect was comparable in magnitude to those of isoniazid and rifampin over the same period.

The delayed onset of the effect of the compound in comparison to rifampin and isoniazid might be caused by the mechanism of action. As the compound works on the ATP synthase inhibiting the generation of new energy, it is tempting to conclude that after depletion of the available energy pool the bacteria start to become affected. However, this thinking remains speculation while we still have limited information.

The results are an encouraging read - especially when considering the closing comment of the authors in the introductory section of their article: "TMC207/R207910 is the first novel anti-TB compound to be studied in patients in nearly 4 decades."

You can read the abstract of the paper here.

Posted in Tuberculosis