Rdea594

[Admin]

Press Release:
Ardea Biosciences' Advances RDEA806 Into Phase 2a Proof-of-Concept Study for Gout

Ardea Biosciences, Inc. (Nasdaq: RDEA) today announced that it has received regulatory approval to begin a Phase 2a proof-of-concept clinical trial evaluating RDEA806 in gout patients with hyperuricemia. Gout, also known as metabolic arthritis, is a painful and debilitating disease caused by abnormally elevated levels of uric acid in the blood stream, and is the most common form of inflammatory arthritis in men over 40. The Company also announced that gout specialist, Dr. Fernando Perez-Ruiz in Spain, will be the newest member of its inflammatory disease scientific advisory board (SAB).

Ardea previously announced the designation of RDEA594, a major metabolite of RDEA806, the Company's lead human immunodeficiency virus (HIV) development compound, as its lead development candidate for the treatment of patients with gout. RDEA594 does not have antiviral activity, but is believed to be responsible for essentially all of the uric acid lowering effects seen with RDEA806. Uric acid lowering effects have been observed following administration of RDEA806 in Phase 1 and Phase 2 clinical trials that included over 100 subjects.

"The Phase 2a trial should allow us to confirm RDEA594's activity in the target population of patients with gout using its prodrug, RDEA806. Enrollment in the Phase 2a trial should begin shortly and we are on track to initiate a Phase 1 trial with RDEA594 in the second half of this year," said Barry D. Quart, PharmD, Ardea Biosciences' President and CEO. "We also are extremely pleased to add Dr. Fernando Perez-Ruiz to our inflammatory diseases SAB. Dr. Perez-Ruiz has extensive experience treating gout patients with drugs of the same class as RDEA594."

The Phase 2a randomized, double-blind, dose ranging, efficacy and safety trial will be conducted in academic medical centers in Europe and Canada. In this trial, we plan to evaluate the serum uric acid (sUA) level, pharmacokinetics, safety and tolerability of two different dose regimens of RDEA806 versus placebo in establishing normal sUA concentrations in gout patients with hyperuricemia (greater than or equal to 8.0 mg/dl). The primary efficacy endpoint is the proportion of subjects whose sUA level is less than 6.0 mg/dl following four weeks of treatment.

Dr. Fernando Perez-Ruiz is an Assistant Head of the Rheumatology Division at the Hospital de Cruces in Vizcaya, Spain. He received his medical degree from the Basque Country University in Bilbao, Spain, and a PhD from Barcelona University, Spain. Board-certified in Rheumatology, Dr. Perez-Ruiz is a member of the American College of Rheumatology and Spanish Society for Rheumatology and has collaborated with the European League Against Rheumatism (EULAR) Task Force for Gout and with the Outcome Measures for Rheumatic Arthritis Clinical Trials (OMERACT) group for chronic gout. He serves on the editorial boards of Arthritis Rheumatism (Care & Research), Bone Joint Spine, and Reumatologia Clinica and serves as a reviewer for more than 20 international journals. His research interests include crystal-induced arthritis, especially gout, but he has also investigated lupus, rheumatoid arthritis and fibromyalgia. Dr. Perez-Ruiz has published more than 80 articles on topics related to rheumatology, and most frequently to hyperuricemia and gout.

[Admin]

Press release:
Ardea Biosciences Initiates Phase 2b Clinical Trial of RDEA594, Lead Product Candidate for the Treatment of Gout
RDEA684 Is Selected as Next-Generation Development Candidate for Treatment of Gout

Ardea Biosciences, Inc. (Nasdaq:RDEA) today announced that it has initiated a Phase 2b clinical trial of RDEA594, its lead product candidate in development for the management of hyperuricemia and gout. The Company also announced the selection of RDEA684, a next-generation URAT1 inhibitor, as a development candidate for the same indication.

The randomized, double-blind, placebo-controlled, dose-response study will evaluate the safety and serum urate-lowering effects of 200, 400 and 600 mg of RDEA594 in a total of 140 gout patients with hyperuricemia (uric acid levels of 8 mg/dL or more). The primary efficacy endpoint is the proportion of patients whose serum urate level is less than 6.0 mg/dL following four weeks of treatment. This study will be conducted at multiple sites in Europe and North America, with initial results expected by the end of 2009. The remaining studies in the planned Phase 2 program, including a Phase 2 study evaluating RDEA594 as an add-on to allopurinol in patients not responding adequately to allopurinol alone, a drug-drug interaction study with febuxostat (Uloric®, Takeda Pharmaceutical Company Limited; Adenuric®, Ipsen), and a study in patients with renal impairment, are expected to begin shortly.

“Our Phase 2 program is designed to demonstrate RDEA594’s broad clinical potential in a wide spectrum of gout patients, including first-line use and as add-on therapy in patients not achieving an adequate response to either allopurinol or febuxostat, and in patients with varying degrees of renal impairment,” commented Barry D. Quart, Pharm.D., Ardea’s president and chief executive officer. “The FDA approval of febuxostat earlier this year and the recent recommendation by the FDA’s Arthritis Advisory Committee for approval of pegloticase (Krystexxa™, Savient Pharmaceuticals) for treatment-refractory gout has demonstrated the importance of new urate-lowering therapies for treatment of patients suffering from gout.”

About RDEA594 and RDEA684

RDEA594, our lead product candidate for the treatment of hyperuricemia and gout, is a selective URAT1 transporter inhibitor that has successfully completed a Phase 2a proof-of-concept study in gout patients with hyperuricemia, as well as single- and multiple-ascending-dose Phase 1 studies in normal, healthy volunteers. Over 300 people have safely received RDEA594, either by direct administration or through administration of RDEA806, its prodrug. RDEA684, a next-generation URAT1 inhibitor, has been selected as a development candidate and has entered preclinical development in anticipation of a first-in-human clinical trial, which is expected to begin in 2010. Based on preclinical results, RDEA684 demonstrates many of the same positive attributes as RDEA594, but with more than 170-times greater potency against the URAT1 transporter.

[Admin]

This clinical trial has just been registered:

Gout Dose Response Study

Information provided by: Ardea Biosciences, Inc.
ClinicalTrials.gov Identifier: NCT00955981

To compare the proportion of subjects whose serum urate (sUA) level is < 6.0 mg/dL after 28 days of dosing by treatment group.

[Admin]

Press Release:
Ardea Biosciences Announces Additional Positive Results from a Phase 2a Study of RDEA594 at the 2009 ACR/ARHP Annual Scientific Meeting
RDEA594 Significantly Reduced Serum Urate Levels in Gout Patients and Was Well Tolerated

Ardea Biosciences, Inc. (Nasdaq: RDEA) today announced additional positive results from the completed first cohort of an ongoing Phase 2a, proof-of-concept study of RDEA594, its lead product candidate for the treatment of hyperuricemia and gout. These results, as well as data from a preclinical drug-drug interaction study demonstrating RDEA594's potential to be used in combination with allopurinol and febuxostat (Uloric(R), Takeda Pharmaceutical Company Limited; Adenuric(R), Ipsen), are being presented today at the 2009 American College of Rheumatology (ACR)/Association of Rheumatology Health Professionals (ARHP) Annual Scientific Meeting in Philadelphia, Pennsylvania.

In the first cohort of this small placebo- and active-controlled study of 21 gout patients with hyperuricemia (serum urate greater-than or equal to 8 mg/dL), 11 patients were randomized to blinded RDEA594 200 mg once-daily (qd) for one week followed by RDEA594 400 mg qd for one week, 5 patients were randomized to blinded placebo for two weeks and 5 patients were randomized to open-label allopurinol 300 mg qd for two weeks. All patients receiving RDEA594 experienced a dose-related reduction in uric acid levels in their blood. Patients who excrete less than normal amounts of uric acid make up approximately 90% of the gout patient population and are the primary target for treatment with RDEA594. In this study, the response rate (response defined as serum urate to < 6 mg/dL) to RDEA594 in these patients was 60% (6/10) after two weeks of treatment. A majority of patients randomized to RDEA594 also had mild to moderate renal impairment (Creatinine Clearance by Cockcroft-Gault method = 50-89 ml/min) at baseline and 86% of those patients responded to RDEA594 at two weeks.

RDEA594 increased urinary excretion of uric acid in the under-excretor patients in this study to pre-treatment levels seen in normal healthy volunteers in prior studies. Avoiding excessive clearance of uric acid should reduce the risk of renal toxicity. RDEA594 was also well tolerated in this study, with no serious adverse events and no premature discontinuations due to adverse events in patients receiving RDEA594.

In the ongoing second cohort of this trial, 6 gout patients with hyperuricemia (serum urate greater-than or equal to 9 mg/dL) will receive allopurinol 300 mg qd for one week followed by the addition of RDEA594 or placebo for two more weeks.

Preclinical models did not show any drug-drug interactions between RDEA594 and either allopurinol or febuxostat. Ongoing studies in humans will provide additional evidence to support the potential use of these combinations. An update on animal safety studies was also presented with recent results from a 3-month and 6-month assessment of chronic toxicity in rats and monkeys, respectively, showing no organ toxicity with RDEA594. In particular, no renal toxicity was noted in clinical chemistry, gross pathology or histopathology at doses up to 300 mg/kg/day.

"RDEA594 continues to move through clinical development with an impressive efficacy and safety profile. The significant activity observed in patients with mild to moderate renal impairment, a substantial group of gout patients that are not effectively treated with allopurinol, is extremely encouraging," commented Barry D. Quart, PharmD, Ardea's president and chief executive officer. "Results presented today provide an important first look at what we expect to see in the larger single-agent Phase 2b dose-response trial now underway, as well as validation of the doses selected for all studies in the Phase 2 program."