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Antiviral activity of RDEA806, a novel HIV non-nucleoside reverse transcriptase inhibitor, in treatment of näive HIV patients

Presented by Graeme Moyle, United Kingdom.

G. Moyle1, M. Boffito1, K. Manhard2, B. Sheedy2, V. Hingorani3, L.-T. Yeh2, B. Quart2

1Chelsea and Westminster Hospital, Department of HIV and Genitourinary Medicine, London, United Kingdom, 2Ardea Biosciences, Inc., San Diego, United States, 3Vanguard Healthsciences, Inc, San Diego, United States

Background: RDEA806 is an NNRTI in development for the treatment of HIV infection. Preclinical testing has shown an improved resistance profile, a higher barrier to resistance, and a lack of reproductive toxicity. In Phase 1 studies, RDEA806 was well tolerated with single or multiple doses, with no drug related CNS toxicity. A phase 2a study was conducted to evaluate the antiviral activity of RDEA806 monotherapy in antiretroviral näive HIV patients.
Methods: A Phase 2a, randomized, double-blind, placebo-controlled, proof-of-concept trial was conducted in 48 näive HIV-infected male patients randomized to receive RDEA806 or placebo in each of 4 dose cohorts (9 active and 3 placebo per cohort) for 7 days and a single morning dose on Day 8 for pharmacokinetic determination. Cohorts 1 and 2 received RDEA806 as a modified release capsule fasting at 400 mg twice daily (BID) or 600 mg once daily (QD); Cohorts 3 and 4 received RDEA806 as an enteric coated tablet at 800 mg QD fed or 1000 mg QD fasting. Plasma viral load, safety, and tolerability were assessed.
Results: Baseline viral load ranged from 4880 to 879,000 copies/ml. RDEA806 produced a rapid decline in viral load with median reductions at nadir of 1.8 to 2.0 log copies/ml, compared to a 0.09 log copies/ml reduction for placebo. Viral load reductions observed with QD dosing of the enteric-coated tablet were comparable to the 400 mg BID dosing of the modified release capsule. There was no drug-related rash and no difference between drug and placebo in CNS side effects. Overall, RDEA806 was well tolerated; no serious adverse events or premature discontinuations occurred.
Conclusions: RDEA806 was well tolerated and produced robust antiviral activity when dosed as monotherapy. Once daily dosing with the new enteric-coated tablet produced equivalent activity to BID dosing, and sufficient antiviral activity to proceed into a Phase 2b study.

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