Ardea Biosciences, Inc. Reports Additional Positive Phase 2a Results for Lead HIV Candidate, RDEA806
SAN DIEGO, June 25 -- Ardea Biosciences, Inc. today announced additional positive results from its completed Phase 2a proof-of-concept monotherapy study of RDEA806, its novel investigational non-nucleoside reverse transcriptase inhibitor (NNRTI), in patients with human immunodeficiency virus (HIV).
These additional results demonstrated that once-daily dosing with the enteric-coated tablet formulation of RDEA806 resulted in significant reductions in plasma viral load that were consistent with results previously presented with twice-daily dosing of the capsule formulation in the same study. All dosing regimens tested in the study were well tolerated. Ardea's lead investigator plans to present the full data from this study at a medical conference later this year.
"RDEA806's robust antiviral potency, combined with its excellent tolerability profile in over 130 healthy volunteers and HIV-infected patients treated in clinical studies to-date, make RDEA806 a promising candidate for further investigation as a first-line agent for the treatment of HIV," said Dr. Graeme Moyle, Director of HIV Research, Chelsea and Westminster Hospital, and a lead investigator in the completed Phase 2a trial and planned Phase 2b study.
Phase 2a Clinical Trial Design & Top-line Results
The Phase 2a randomized, double-blind, placebo-controlled trial evaluated the antiviral activity, pharmacokinetics, safety and tolerability of once- and twice-daily oral dosing regimens of RDEA806 versus placebo in 48 HIV-positive patients who were naive to antiretroviral treatment. Nine out of 12 patients in each of four cohorts received RDEA806. The primary efficacy end point was the change from baseline in plasma viral load. Top-line results from all four cohorts showed the following:
-- The median reduction in plasma viral load at nadir was 1.9 - 2.1 log copies/ml (placebo adjusted) for all four treatment cohorts.
-- Patients receiving either 800 mg or 1000 mg once daily with the enteric-coated tablet formulation, and patients receiving 400 mg twice daily with the capsule formulation, experienced a 1.8 - 1.9 log median reduction in plasma viral load (adjusted for placebo) on Day 8; the 600 mg capsule formulation given once daily produced a 1.4 log median reduction (adjusted for placebo) at this time point.
-- There were no serious adverse events, ECG-related adverse events, or drug-related rash reported in any cohort. The incidence of CNS side effects was similar between drug and placebo. Administration of the highest dose on an empty stomach showed an increase in gastrointestinal side effects, but these effects were generally transient and mild.
-- There were no premature discontinuations in any cohort.
-- Based on the results generated in this trial, the doses planned for the Phase 2b program will be 600 mg, 800 mg and 1000 mg once daily with the enteric-coated tablet given with or without food.
"We are very pleased to announce the successful completion of the Phase 2a program with RDEA806," said Barry D. Quart, PharmD, Ardea's President and CEO. "Based on the excellent antiviral activity observed with once-daily dosing of the enteric-coated oral formulation, we plan to proceed in the third quarter of this year with a multi-national Phase 2b study comparing 600 mg, 800 mg and 1000 mg once daily doses of RDEA806 to efavirenz (SUSTIVA(R)) in first-line patients receiving background treatment with Truvada(R) (emtricitabine and tenofovir)."
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 may have important competitive advantages. These include the potential for potent antiviral activity against a wide range of HIV viral isolates, including those that are resistant to efavirenz (Sustiva(R)) and other currently available NNRTIs; a high genetic barrier to resistance; no reproductive toxicity based on animal studies; 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
Ardea Biosciences, Inc., of San Diego, California, is a biotechnology company focused on the discovery and development of small-molecule therapeutics for the treatment of HIV, cancer and inflammatory diseases, including gout. We have four drug candidates in clinical trials and others in preclinical development and discovery. Our most advanced development candidate is RDEA806, a non-nucleoside reverse transcriptase inhibitor (NNRTI), which has completed a Phase 2a study for the treatment of HIV. We have evaluated our second-generation NNRTI for the treatment of HIV, RDEA427, in a human micro-dose pharmacokinetic study and have selected it as a development candidate. RDEA594, our lead development candidate for the treatment of gout, is in preclinical development and is believed to be an inhibitor of the URAT1 transporter in the kidney, which is responsible for regulation of uric acid levels. We are evaluating our lead MEK inhibitor, RDEA119, in a Phase 1 study in advanced cancer patients, as well as in a Phase 1 study in normal healthy volunteers as a precursor to trials in patients with inflammatory diseases. Lastly, we have evaluated our second- generation MEK inhibitor for the treatment of cancer and inflammatory diseases, RDEA436, in a human micro-dose pharmacokinetic study and have selected it as a development candidate.
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 our goals, including the expected properties and benefits of RDEA806, RDEA427, RDEA594, RDEA119, RDEA436 and our other compounds and the results of preclinical, clinical and other studies. Risks that contribute to the uncertain nature of the forward-looking statements include: risks related to the outcome of preclinical and clinical studies, risks related to regulatory approvals, delays in commencement of preclinical and clinical studies, and costs associated with our drug discovery and development programs and business development activities. These and other risks and uncertainties are described more fully in our most recently filed SEC documents, including our Annual Report on Form 10-K and our 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. We undertake no obligation to update such statements to reflect events that occur or circumstances that exist after the date on which they were made