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RDEA806, a Novel HIV Non-Nucleoside Reverse Transcriptase Inhibitor, Shows Positive Outcome in Treatment of Naive HIV Patients
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Reported by Jules Levin, ICAAC/IDSA 25-28 October 2008 Washington, DC
G. Moyle, M. Boffito, Z. Shen, K. Manhard, B. Sheedy, V. Hingorani, M. Nguyen, T. Nguyen, B. Quart, L. Yeh, V. Ong
RDEA806 AUTHOR CONCLUSIONS
--Well tolerated with robust antiviral effect across all doses
--Tmax ranged from 2-6 hours, half-life ~9-12 hours
--Antiviral activity similar between 800 mg QD and 400 mg BID
--No significant induction of CYP3A4, indicating a low potential for drug interactions
--Significant reduction in uric acid across all doses, with no effect on the renal excretion of tenofovir.
--Phase 2b in antiretroviral treatment-naïves planned to begin this quarter
Preclinical Background
--RDEA806 is a potent (EC50wt= 3 nM), selective HIV NNRTI designed to maintain activity against the most common mutations observed with efavirenz (EC50K103N= 2.3 nM)
--High barrier to resistance
--Cytotoxicity selectivity index > 9,000
--Highly protein bound (~99.5%)
--Limited metabolism by CYP450 (none by 2B6) and no inhibition or induction of CYP450
--Completed animal reproduction studies have shown no evidence of teratogenicity or impairment of fertility
--Highly water soluble, allowing for preparation of easy to swallow tablets easy to swallow tablets
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