Drug Discovery & Development
Idenix’s development program includes IDX899, a novel non-nucleoside reverse transcriptase inhibitor (NNRTIs) to treat HIV, which is currently in phase I/II clinical trials. NNRTIs are important components of effective antiretroviral therapy (ART) combination regimens for the treatment of HIV-1 infected individuals1.
In in-vitro preclinical studies, IDX899 has demonstrated potent antiviral activity, a favorable toxicology profile and potential for once-daily dosing. Also in-vitro, IDX899 exhibited potent activity against established NNRTI-resistant clinical isolates, and, compared to efavirenz, the emergence of IDX899-resistant HIV-1 isolates was slower and required several mutations suggesting a higher barrier to resistance for IDX899.
A phase I/II clinical trial evaluated the safety, tolerability and antiviral activity of IDX899 in treatment-naive HIV-1-infected patients. Four cohorts of 800 mg, 400 mg, 200 mg and 100 mg were completed with ten patients randomized 8:2 in each cohort to receive oral once-daily IDX899 or matching placebo, respectively, for seven days. Patients receiving once-daily IDX899 achieved a mean plasma viral load reduction of approximately 1.8 log(10) after seven days of treatment in each of the 800 mg, 400 mg, 200 mg and 100 mg dosing cohorts. No treatment-related serious adverse events were reported for any of the patients receiving IDX899 and no patients discontinued the study. Also, there were no discernable patterns in adverse events between treatment groups and there were no laboratory abnormalities during the treatment period. These data demonstrate potent antiviral activity and a favorable safety profile at all tested doses.
1 Guidelines for the Use of Antiretroviral Agents in HIV-1-Infected Adults and Adolescents, DHHS Panel on Antiretroviral Guidelines for Adults and Adolescents
XVII International Drug Resistance Workshop Materials
6.12.08 Idenix HIV Drug Resistance Press Release
Murphy et al, HIV Drug Resistance Workshop June 12, 2008
Presentation