Ardea Biosciences Announces Positive Interim Phase 2a Results For Lead Gout Drug, RDEA594

Main Category: Gout
Also Included In: Clinical Trials / Drug Trials
Article Date: 14 Jun 2009 - 3:00 PDT

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Ardea Biosciences, Inc. (Nasdaq:RDEA) announced positive interim results from an ongoing Phase 2a, proof-of-concept study of RDEA594, its lead product candidate for the treatment of hyperuricemia and gout, as well as additional positive results from completed Phase 1 studies of RDEA594 in normal, healthy volunteers. The Phase 1 results, along with additional preclinical data, were presented at the Annual European Congress of Rheumatology hosted by the European League Against Rheumatism (EULAR) in Copenhagen, Denmark.

In late April 2009, the Company initiated a placebo- and active-controlled, proof-of-concept study of RDEA594 in gout patients with hyperuricemia (uric acid ≥ 8 mg/dL). This study is now fully enrolled and the majority of the 20 patients have completed the first week of dosing. Patients received RDEA594 200 mg once daily (QD) for the first week, followed by 400 mg QD for the second week. An immediate release (IR) capsule formulation, administered under fed conditions, was used in this study. Of the first 7 patients randomized to RDEA594 to reach 8 days of dosing (first day after dose increased to 400 mg QD), 6, or 86%, were responders, as defined by the achievement of target uric acid concentrations of less than 6 mg/dL. This compares to zero out of 4 patients randomized to placebo and 2 out of 3 patients randomized to a standard dose of allopurinol (300 mg QD) to reach 8 days of dosing. On average, RDEA594-treated patients achieved a 40% reduction in serum urate levels by this early time point. Dosing in this Phase 2a study is expected to be completed in late June 2009, with full results to be presented at an upcoming scientific conference. RDEA594 has been well tolerated in this study, with no serious adverse events and no premature discontinuations due to adverse events.

Results from two completed, randomized, double-blind, placebo-controlled, Phase 1 studies were presented at EULAR that included data from 98 adult male subjects, of which 76 received RDEA594 at doses from 5 mg to 600 mg for 1 to 10 days. Statistically significant, dose-dependent reductions in serum urate of up to 45% were demonstrated in the multiple-ascending-dose study, which evaluated QD doses of RDEA594 100 mg oral solution and 200 and 400 mg IR capsules given fasted or placebo over a 10-day dosing period. Administration of the IR capsule with a standard breakfast, as done in the Phase 2a study, improved the pharmacokinetic profile of the drug and increased the reduction in uric acid compared to fasted conditions. RDEA594 was well tolerated at all dose levels tested, including single doses of an oral solution up to 600 mg, multiple doses of the IR capsules up to 400 mg QD, and multiple doses of an experimental extended-release tablet up to 600 mg QD. Adverse events (AEs) were mild to moderate in severity with no change with increasing dose, and no serious adverse events or discontinuations due to AEs.

"These very encouraging interim data from our Phase 2a study have confirmed the activity and safety of RDEA594 in gout patients and our formulation and dose selections for the upcoming Phase 2b program," commented Barry D. Quart, PharmD, Ardea's president and chief executive officer. "With the RDEA594 proof-of-concept data now in hand and our recent experience rapidly enrolling gout patients, we look forward to successfully completing major components of our Phase 2b evaluation of RDEA594 as planned in the fourth quarter of 2009."

"The Phase 1 and interim Phase 2a results are very encouraging and provide a strong basis for moving RDEA594 into larger Phase 2b studies," commented John S. Sundy, MD, PhD, associate professor of medicine and head of the Section of Allergy and Clinical Immunology in the Division of Pulmonary, Allergy and Critical Care Medicine at Duke University Medical Center and a member of Ardea's scientific advisory board.

The EULAR posters are available on the Company's website (http://www.ardeabio.com) under the titles, "Safety, Pharmacokinetics, and Serum Uric Acid Lowering Effect of RDEA594, A Novel Uricosuric Agent, In Healthy Volunteers" and "RDEA594: A Potent URAT1 Inhibitor Without Affecting Other Important Renal Transporters, OAT1 and OAT3".

About RDEA594

RDEA594 is our lead product candidate for the treatment of hyperuricemia and gout. RDEA594 is an inhibitor of the URAT1 transporter in the kidney, which is responsible for the regulation of uric acid levels. Over 300 people have safely received RDEA594, either by direct administration or through administration of RDEA806, its prodrug.

Source
Ardea Biosciences, Inc.