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Phase 2 Efficacy Study in Gout Patients to Start in the First Half of 2008
CARLSBAD, CA, USA | November 28, 2007 | 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 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).
Hyperuricemia in HIV
There is a high prevalence of hyperuricemia (elevated uric acid levels) in the HIV population. According to one large study, hyperuricemia is observed in 41% of HIV patients (2). Furthermore, HIV protease inhibitors were a significant risk factor for hyperuricemia (p < 0.003) in this study. "While we plan to target the uric acid-lowering effect demonstrated with RDEA806 administration principally at the gout opportunity, we also continue to move forward aggressively with our HIV development program. Reducing uric acid should be an added benefit to many HIV patients," said Dr. Quart.
Anticipated Milestone Events
The Company also reiterated today its goal to achieve its previously announced development milestone targets. These, together with the gout-related milestone targets announced today, include the following:
-- Initiation of a Phase 2a proof-of-concept trial in HIV patients with our lead NNRTI, RDEA806, in the fourth quarter of 2007;
-- Initiation of a Phase 1 trial in advanced cancer patients with our lead mitogen-activated ERK kinase (MEK) inhibitor, RDEA119, in the fourth quarter of 2007;
-- Assessment of a next-generation NNRTI in a first-in-human micro-dosing study in the fourth quarter of 2007;
-- Assessment of a next-generation MEK inhibitor in a first-in-human micro-dosing study in the fourth quarter of 2007;
-- Completion of the HIV Phase 2a trial of RDEA806 in the first quarter of 2008;
-- Initiation of a Phase 2 efficacy trial in gout patients with RDEA806 in the first half of 2008; and
-- Initiation of a clinical program to evaluate RDEA119 in inflammatory diseases in the first half of 2008.
"We are excited about the continued progress of our deep product pipeline," stated Dr. Quart. "By the end of this year, we hope to have four novel molecules in the clinic for three distinct indications, with an additional one-to-two indications in inflammatory diseases planned for the first half of next year."
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 have active development programs with four new chemical entities (NCEs) in the clinic for three distinct indications by the end of 2007, with an additional one-to-two indications in inflammatory diseases planned for the first half of 2008.
Ardea's most advanced clinical development programs include: RDEA806, the Company's lead NNRTI for the treatment of HIV, which is expected to enter a Phase 2a clinical trial in the fourth quarter of 2007; RDEA119, a mitogen-activated ERK kinase (MEK) inhibitor for the treatment of cancer and inflammatory diseases, which is expected to enter a Phase 1 clinical trial in advanced cancer patients in the fourth quarter of 2007; and RDEA806 for gout, which is expected to enter a Phase 2 efficacy trial in the first half of 2008. Ardea also is developing a next-generation NNRTI and a next-generation MEK inhibitor, both of which are scheduled to enter first-in-human studies in the fourth quarter of 2007.
(1) New England Journal of Medicine 2005;353;23:2450-61.
(2) Nephron Physiol 2006;103:p131-p138.
SOURCE: ARDEA BIOSCIENCES |
