48-week Data on TMC 125, a Next Generation Experimental NNRTI from Tibotec Pharmaceuticals

Tibotec Pharmaceuticals presented 48 week efficacy and safety data on TMC125 a next-generation non-nucleoside reverse transcriptase inhibitor (NNRTI) at the Toronto meeting this week. TMC125 is currently being investigated in phase 3 trials (DUET 1 and 2) in treatment-experienced adult patients.

The presented data were the final 48 week analysis of study TMC125-C223, a phase 2b dose-finding, randomized, partially-blinded study in adult HIV patients with substantial treatment experience, documented evidence of NNRTI resistance and 3 or more PI mutations.

A total of 199 patients were randomized to TMC 125 (400 mg or 800 mg bid) (n=159) plus background regimen or best available control regimen (n=40).

Results

Intent to treat analysis showed that the mean change from baseline in viral load at week 48 was -0.88, -1.01 and -0.14 log10 copies/ml in the TMC125 400mg and 800 mg bid and active control groups.

A decrease from baseline in plasma viral of at least 1 log10 copies/ml was achieved by 31%, 34% and 8% of patients respectively.

In these patients with NNRTI resistance, the viral load reduction in patients receiving TMC125 400mg or 800mg bid in combination with an optimized background regimen (OBR) was significantly greater than in the active control at 48 weeks, p=0.018 and p=0.002 respectively.

Ninety eight percent of control group patients had discontinued treatment by 48 weeks, compared with 38% of TMC125 patients.

The comparison of adverse events (AEs) and serious AEs (SAEs) between the TMC125 arms and the control group is confounded, as by week 48 98% of patients in the control group had discontinued the majority for poor virologic response.

The most common adverse events (AEs) were diarrhoea, pyrexia and rash which were 22%, 20% and 20%, respectively, for the TMC125 groups compared with 15%, 10% and 8% for the active control group. Overall, 27% of TMC125 and 18% of control patients reported at least one serious adverse event (SAEs); 4 of these SAEs were classified as possibly related to TMC125.

In conclusion, the authors write, "In this study, TMC125 showed high rates of sustained efficacy at 48 weeks in heavily pre-treated patients. The analysis of response by baseline resistance shows that TMC125 retains activity in the presence of multiple NNRTI mutations where current NNRTIs are not expected to be effective."

08/18/06

Sources

C Cohen, C Steinhart, D Ward, and others. Efficacy and safety results at 48 weeks with the novel NNRTI, TMC125, and impact of baseline resistance on the virologic response in study TMC125-C223. 16th International AIDS Conference. August 13-18, 2006. Toronto, Canada. Abstract TUPE0061.

Tibotec Pharmaceuticals. 48 Week Data on Investigational Antiretroviral TMC125 from Tibotec. Press Release. August 15, 2006.