TMC278, an investigational nonnucleoside reverse transcriptase inhibitor (NNRTI) reputed to have a high barrier to resistance, passed a crucial step in clinical development—a seven day monotherapy test in treatment-naive patients. The median viral load drop measured 1.2 log10 copies/mL (more than 10-fold), reported Frank Goebel, MD, from Munich’s Ludwig Maximilians University, at the Twelfth Conference on Retroviruses and Opportunistic Infections held in Boston, Massachusetts (Goebel 2005).
With activity against some NNRTI-resistant virus (de Bethune 2005), TMC278 is the second of two NNRTIs under development at Tibotec in Mechelen, Belgium. The drug’s lengthy 38-hour half-life could make once-daily dosing possible.
Dr. Goebel and colleagues in Russia and the United Kingdom randomised 47 treatment-naive individuals to placebo or 25mg, 50mg, 100mg, or 150mg TMC278 given once daily for seven days as an oral solution. Study participants began treatment with a median viral load of 4.5 log10 copies/ml (range 3.5-5.9 log10 copies/ml) and a median CD4+ cell count of 292 cells/mm3 (range, 29-590 cells/ mm3).
After seven days, the median HIV-1 load dropped 1.29 logs with TMC278 25mg, 1.23 logs with 50mg, 1.07 logs with 100mg, and 1.17 logs with 150mg , with no change in the placebo group (P value vs placebo
No one stopped treatment because of toxicity in this brief study, and no serious side effects were reported. The median CD4+ cell count climbed 55 cells/mm3 in seven days.
A multinational phase 2b dose-finding study begins in March 2005.
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Goebel F et al. TMC278: potent anti-HIV activity in antiretroviral therapy-naive patients. Twelfth Conference on Retroviruses and Opportunistic Infections, Boston, abstract 160, 2005.
de Bethune MP et al. TMC278, a new potent NNRTI with an increased barrier to resistance and good pharmacokinetic profile. Twelfth Conference on Retroviruses and Opportunistic Infections, Boston, abstract 556, 2005.