Ardea Biosciences, Inc. (RDEA)

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Ardea Biosciences, Inc. Announces New Clinical Development Program Directed Toward the Treatment of Gout
Wednesday November 28, 8:00 am ET
- RDEA806 Shown to Produce Statistically Significant, Dose-Dependent Reduction in Serum Uric Acid in Phase 1 Clinical Study
- Phase 2 Efficacy Study in Gout Patients to Start in the First Half of 2008

CARLSBAD, Calif., Nov. 28 /PRNewswire-FirstCall/ -- Ardea Biosciences, Inc. (Nasdaq: RDEA - News) today announced the initiation of a new clinical development program directed toward the treatment of gout. Gout, also known as metabolic arthritis, is a painful and debilitating disease caused by abnormally elevated levels of uric acid in the blood stream. These abnormally elevated levels lead to the deposition of uric acid crystals in and around the connective tissue of the joints and in the kidneys, leading to inflammation, the formation of disfiguring nodules (tophi), intermittent attacks of severe pain (acute flares), and kidney damage (nephropathy). An estimated 3-5 million people in the U.S. suffer from gout, which is the most common form of inflammatory arthritis in men over 40.

"We are extremely excited to be launching this new development initiative," said Barry D. Quart, Pharm.D., President and Chief Executive Officer. "Gout represents a major medical challenge in the U.S. and throughout the world, and, with no new treatments approved by the U.S. Food and Drug Administration for the underlying cause of gout in the past 40 years, there is a significant need for new therapeutic agents."

Phase 1 Experience

Earlier this year, Ardea conducted a comprehensive Phase 1 program in 98 healthy volunteers to evaluate the safety and pharmacokinetics of RDEA806, its lead non-nucleoside reverse transcriptase inhibitor (NNRTI) for the potential treatment of HIV. The Phase 1 program included a double-blind, placebo-controlled, multiple-ascending-dose (MAD) study in which 24 healthy volunteers received one of three doses of RDEA806 or placebo for 10-14 days. As reported earlier (http://www.ardeabio.com/publications_posters.html), RDEA806 was safe and well-tolerated at all doses evaluated with no serious adverse events or clinically significant laboratory or ECG abnormalities. Furthermore, a trend toward a reduction in plasma cholesterol and triglyceride levels was reported.

Further analysis of the data from the MAD study showed a statistically significant, exposure-dependent reduction in serum uric acid (SUA). In the dose group that resulted in the highest plasma drug levels (400 mg modified-release capsule twice daily), there was a 50.9% placebo-adjusted reduction in SUA (p < 0.001). The following table summarizes the results by dose group.

Effect of RDEA806 on Serum Uric Acid (SUA) Levels in Phase 1 MAD Study
Mean SUA Level (mg/dL)
Baseline Day 3 Day 10/14[1] Change P Value[2]
Placebo 5.66 6.12 5.78 +3.0 %
300 mg BID [3] 6.19 4.50 4.15 -31.6 % < 0.001
500 mg BID [3] 4.94 2.94 3.06 -38.1 % < 0.001
400 mg MR BID [3][4] 5.25 2.99 2.80 -47.9 % < 0.001


[1] Patients receiving 300 mg and 500 mg BID were dosed for
14 days; patients receiving 400 mg MR BID were dosed for 10 days.
[2] ANCOVA model for the change from baseline versus placebo.
[3] BID = twice daily.
[4] MR= modified-release capsules. This dose group achieved the
highest plasma drug levels.


The magnitude of the uric acid reduction correlates with the individual's baseline uric acid level, such that the higher the baseline uric acid level, the larger the absolute uric acid reduction. On the last day of dosing, this correlation is highly statistically significant (p=0.004). To this end, the volunteers who met the accepted definition of hyperuricemia at baseline (SUA greater than 6.8 mg/dL, the limit of uric acid solubility in serum) experienced the greatest decrease, an average of 3.2 mg/dL on the last day of dosing.

Development Plan

Ardea is preparing to initiate a Phase 2, dose-ranging clinical efficacy study in gout patients with hyperuricemia in the first half of 2008. The Company is currently investigating the active moiety responsible for this pharmacological effect and its mechanism of action, as these may influence further development plans.

Current Treatment Options

Despite the well-understood etiology of gout, current treatment options are limited. There have been no new therapies approved by the FDA for the treatment of hyperuricemia associated with gout in the past 40 years, and the most-prescribed, FDA-approved pharmaceutical agent, allopurinol, has significant limitations. According to a large, randomized, clinical study, only 21% of patients receiving allopurinol achieve their treatment target, while 8% experienced serious adverse events (1).

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