At the 17th International AIDS Conference in Mexico City Thursday, Moyle G et al, and Zala C, presented data on two novel non-nucleoside reverse transcriptase inhibitor (NNRTI) agents in development that represent promising future treatment options.
RDEA806 is a novel NNRTI with an improved resistance profile, high genetic barrier to resistance and lack of reproductive toxicity in preclinical development. In Phase-I studies it has been found to be well-tolerated and without CNS toxicity.
Graeme Moyle presented findings on Phase IIA studies (THAB0403) which evaluated the efficacy of RDEA806 as monotherapy in a placebo controlled double-blind trial in 48 HIV-positive, antiretroviral naïve subjects using four different dosing strategies over eight days. It was found to be well tolerated, with rapid viral load reductions of 1.8-2.0 log copies/mL. Viral load reductions were similar for both daily enteric-coated tablets and twice daily modified release capsules. Phase IIB studies will move forward using a once-daily enteric-coated formulation.
IDX899 is another novel NNRTI with potent antiviral activity and a high barrier to resistance in vitro. It has shown favorable pharmacokinetics and safety in healthy volunteer studies. C. Zala (THAB0403) presented data on 30 HIV-positive subjects who received three different doses of IDX899 (800, 400 or 200 mg) or placebo once daily for seven days.
All three doses demonstrated a good virologic response (1.78-1.83 log reduction in HIV-1 RNA levels) and trough levels that exceeded the protein binding adjusted EC90 by more than 5 to 20 fold. There were no discontinuations for adverse events. A 100 mg cohort study has been initiated.
References:
Moyle G, et al. THAB0403: antiviral activity of RDEA806, a novel HIV non-nucleoside reverse transcriptase inhibitor, in treatment naïve HIV patients. Presented at: 17th International AIDS Conference; August 3-8, 2008; Mexico City, Mexico. Abstract THAB0403.
Zala C. THAB0402: IDX899, a novel NNRTI with high barrier to resistance, provides suppression of HIV viral load in treatment naïve HIV-1-infected subjects. Presented at: 17th International AIDS Conference; August 3-8, 2008; Mexico City, Mexico. Abstract THAB0402.
08/07/08
Two NNRTI Agents-in-Development Show Promise
Source: Reporting from Mexico City for PRN News: Anita Radix, MD, MPH and Rona Vail, MD