Ardea Biosciences, Inc. Presents Results of Phase 1 Studies ofRDEA806, a Novel NNRTI for HIV, at 47th ICAAC- RDEA806 safe and well tolerated in single-dose and multiple-dose studies up to 14 days
CHICAGO, September 19, 2007 /PRNewswire-FirstCall/ -- Ardea Biosciences, Inc. today presented the results of Phase 1 single-ascending-dose, multiple-ascending-dose, food-effect and drug-interaction studies of RDEA806, a novel HIV non-nucleoside reverse transcriptase inhibitor (NNRTI), at the 47th Interscience Conference on Antimicrobial Agents and Chemotherapy (ICAAC) [Posters A-1429 and A-1430, Poster Session 160, Antiviral Agents].
Two double-blind, placebo-controlled, Phase 1 studies, conducted in 92 healthy adult male volunteers, of which 78 received RDEA806, demonstrated that RDEA806 was safe and well-tolerated at all doses evaluated with no serious adverse events or clinically significant laboratory or ECG abnormalities. After dosing for up to 14 days at up to 1,000 mg per day, there was no evidence of CNS disturbances or rash, side effects that have been observed with other NNRTIs that are currently marketed or in development. Furthermore, plasma cholesterol and triglyceride levels, which have been shown to increase with many HIV drugs, were stable or decreased during RDEA806 dosing.
The systemic exposure of RDEA806 increased linearly from 50 mg to 600 mg under fasted or fed conditions. The terminal half-life of RDEA806 was up to 11 hours after single doses and up to 13 hours following multiple doses. With doses of 300 mg to 500 mg twice daily, steady-state mean trough concentrations ranged from approximately 150 -- 300 ng/ml, which are well above the EC50 (concentration required for 50% inhibition of viral replication) of RDEA806 (EC50 = 1.67 ng/ml).
Evaluation of the drug-drug interaction liability, in vitro and in vivo, demonstrated that RDEA806 is unlikely to be an inducer or inhibitor of major P450 enzymes or be affected by CYP3A4 inhibitors. When given together with ritonavir, an HIV protease inhibitor and potent inhibitor of CYP3A4, plasma levels of RDEA806 were not significantly altered. These data support preclinical data that RDEA806 may have a reduced potential for drug-drug interactions, which could ultimately lead to a safer and more convenient treatment option for patients and physicians.
"We recognize the need for new HIV drugs that demonstrate potent antiviral activity against a wide range of viral isolates, including those that are resistant to currently available NNRTIs, and that show improved safety, tolerability and reduced potential for drug-drug interactions. Yesterday's presentation of the broad spectrum of antiviral activity of RDEA806 demonstrated its in vitro activity against the majority of HIV strains carrying key reverse transcriptase mutations, including coverage of the 10 most prevalent strains of HIV found in patients failing therapy with efavirenz, marketed as Sustiva(R) by Bristol-Myers Squibb*. Based on this very favorable preclinical profile, the excellent tolerability and the high levels of exposure obtained with oral dosing in Phase 1 studies, we are moving forward to conduct a Phase 2a proof-of-concept study in HIV-infected patients, which we plan to initiate before the end of this year. The terminal half-life of up to 13 hours also gives us the opportunity to evaluate once-daily dosing in Phase 2a," said Barry D. Quart, PharmD, President and CEO.
RDEA806 is a novel non-nucleoside reverse transcriptase inhibitor (NNRTI) for the potential treatment of HIV infection. Based on preclinical and clinical studies to-date, Ardea believes that RDEA806 possesses several attractive properties. These include: potent antiviral activity against a wide range of HIV viral isolates, including those that are resistant to efavirenz (Sustiva(R), Bristol-Myers Squibb) and other currently available NNRTIs; a high genetic barrier to resistance; the potential to be administered in a patient-friendly, oral dosing regimen; limited pharmacokinetic interactions with other drugs; and the ability to be co-formulated with other HIV antiviral drugs.
About Ardea Biosciences, Inc.
Ardea Biosciences is focused on the discovery and development of small-molecule therapeutics for the treatment of viral diseases, cancer and inflammatory diseases. The Company plans to initiate clinical studies on four compounds this year. These include RDEA806, the Company's lead non-nucleoside reverse transcriptase inhibitor (NNRTI) for the treatment of HIV, which recently completed Phase 1 clinical trials, RDEA119, a mitogen-activated ERK kinase (MEK) inhibitor for the treatment of cancer and inflammatory diseases, scheduled to enter Phase 1 clinical trials in the second half of 2007, and a follow-on NNRTI and a follow-on MEK inhibitor, both of which are scheduled to enter first-in-human studies in the fourth quarter of 2007.
Statements contained in this press release regarding matters that are not historical facts are "forward-looking statements" within the meaning of the Private Securities Litigation Reform Act of 1995. Because such statements are subject to risks and uncertainties, actual results may differ materially from those expressed or implied by such forward-looking statements. Such statements include, but are not limited to, statements regarding: Ardea's goals, including its goal of initiating a Phase 2 study of RDEA806 in HIV-infected patients and initiating clinical studies on three additional compounds this year, the expected properties and benefits of its compounds and the results of clinical and other studies. Risks that contribute to the uncertain nature of the forward-looking statements include: risks related to the outcomes of preclinical and clinical trials, risks related to regulatory approvals, delays in commencement of preclinical and clinical tests, and costs associated with internal development and in-licensing activities. These and other risks and uncertainties are described more fully in Ardea's most recently filed SEC documents, including its Annual Report on Form 10-K and Quarterly Reports on Form 10-Q, under the headings "Risk Factors." All forward-looking statements contained in this press release speak only as of the date on which they were made. Ardea undertakes no obligation to update such statements to reflect events that occur or circumstances that exist after the date on which they were made.
* Potent coverage is defined as less than a 10-fold shift in antiviral activity versus wild-type virus. Prevalence of resistant strains based on Bachelor et al. Antimicrob Agents Chemother. 2000 Sep; 44(9): 2475-2484.
Posted: September 2007