SAN DIEGO, May 19 Ardea Biosciences, Inc.(Nasdaq: RDEA) today announced the identification of its lead developmentcandidate for the treatment of patients with gout, RDEA594. Gout is a painfuland debilitating disease that is caused by abnormally elevated levels of uricacid in the blood stream. RDEA594 is a major metabolite in both humans andanimals of RDEA806, the Company's lead human immunodeficiency virus (HIV)development candidate. RDEA594 does not have significant antiviral activity,but is believed to be responsible for essentially all of the uric acidlowering effects seen with RDEA806. Robust uric acid-lowering effects havebeen observed following administration of RDEA806 in Phase 1 and Phase 2clinical trials that included over 100 subjects.
Based on extensive in vitro and in vivo experiments, the Company believesit has elucidated the mechanism by which RDEA594 lowers serum uric acidlevels. RDEA594 exhibits a concentration-dependent inhibitory effect on theURAT1 transporter-mediated uptake of uric acid ex vivo and increases uric acidexcretion in animal models. These effects are believed to result in thelowering of serum uric acid observed with RDEA806. URAT1 is a specific uratetransporter expressed in the kidney responsible for regulation of uric acidlevels, and is a validated target for treatment of hyperuricemia and gout.
"Gout represents a major medical challenge in the United States andthroughout the world, with millions of people affected by this debilitatingcondition," said Barry D. Quart, PharmD, Ardea Biosciences' President and CEO."With the designation of RDEA594 as our clinical candidate for the treatmentof gout, we now expect to have five novel candidates in clinical testingduring the second half of 2008, positioning us with the potential to have abroad-based, late-stage pipeline in 2009. This finding also allows us to focusour future development efforts with RDEA806 on the treatment of HIV."
The Company plans to initiate a Phase 1 clinical study of RDEA594 in thesecond half of this year. As previously announced, the Company also plans toconduct a Phase 2 proof-of-concept clinical study in patients with gout, toconfirm RDEA594's activity in the target population using its prodrug,RDEA806. This study is on track to be initiated in the second quarter of thisyear.
An estimated 3-5 million people in the United States suffer from gout,which is the most common form of inflammatory arthritis in men over 40. Gout,also known as metabolic arthritis, is a painful and debilitating diseasecaused by abnormally elevated levels of uric acid in the blood stream. Theseabnormally elevated levels lead to the deposition of uric acid crystals in andaround the connective tissue of the joints and in the kidneys, leading toinflammation, the formation of disfiguring nodules (tophi), intermittentattacks of severe pain (acute flares), and kidney damage (nephropathy). Whilegout is a treatable condition, there are limited treatment options, and anumber of adverse effects are associated with current therapies. No newtherapies have been approved by the FDA for the treatment of hyperuricemiaassociated with gout in the past 40 years.
RDEA594 is a development candidate that has potential for treating goutpatients with hyperuricemia. RDEA594 is a metabolite of RDEA806, anon-nucleoside reverse transcriptase inhibitor (NNRTI) in development for thetreatment of HIV. In Phase 1 studies with RDEA806 in healthy volunteers,increased urinary excretion of uric acid was observed in the first 24 hoursafter dosing, with statistically significant, exposure-dependent, decreases inserum uric acid of 35% to 50% observed following 10-14 days of dosing.RDEA594 exhibits a concentration-dependent inhibitory effect on theURAT1-mediated uptake of uric acid ex vivo and is believed to be the activemoiety responsible for the uric