Ardea Biosciences, Inc (SAN DIEGO, California), a biotechnology company focused on the discovery and development of small-molecule therapeutics for the treatment of inflammatory diseases, HIV, and cancer, announced that it has received regulatory approval to begin a phase IIa proof-of-concept clinical trial evaluating RDEA806 in gout patients with hyperuricemia. According to the company, no new therapies have been approved by the US FDA in the past 40 years for the treatment of hyperuricemia associated with gout.

Ardea previously announced the designation of RDEA594, a major metabolite of RDEA806 (a nonnucleoside reverse transcriptase inhibitor and its lead HIV development compound), as its lead development candidate for the treatment of patients with gout. RDEA594, believed to be an inhibitor of the URAT1 transporter in the kidney?responsible for regulation of uric acid levels?does not have antiviral activity, but is thought 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 I and II clinical trials that included >100 subjects.

The phase IIa, randomized, double-blind, dose-ranging trial is designed to confirm RDEA594's activity and efficacy using its prodrug RDEA806, in the target population of patients with gout. Enrollment in the phase IIa trial should begin shortly and will be conducted in academic medical centers in Europe and Canada.

In the trial, the company plans 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 ≥8 mg/dL. The primary efficacy endpoint is the proportion of subjects whose sUA level is <6 mg/dL following 4 weeks of treatment. The company intends to initiate a phase I trial with RDEA594 in the second half of 2008.

The company is also evaluating a broad range of compounds that inhibit mitogen-activated ERK kinase (MEK). MEK inhibitors may play an important role in the potential treatment of inflammatory diseases such as rheumatoid arthritis, inflammatory bowel disease, and psoriasis, due to their ability to down-regulate inflammatory cytokines. Preclinical data from lead compounds have shown potential as potent and selective inhibitors of MEK, and have demonstrated the ability to significantly inhibit cytokines, such as TNFα and IL-1ß, which play an important role in inflammation. Preclinical data suggest that these compounds may have favorable pharmaceutical-like properties, including the potential for convenient oral dosing.