Ardea Bio Results Promising

Ardea Biosciences’ Gout Drug Shows Promising Results  

Positive results from phase II a and phase I trials

RDEA594 is Ardea Biosciences’ (RDEA - Analyst Report) lead drug candidate for the treatment of gout. The company recently announced positive interim results from an ongoing phase IIa, proof-of-concept study of RDEA594 for the treatment of hyperuricemia and gout, as well as additional positive results from completed phase I studies of RDEA594 in normal, healthy volunteers.

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 (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 IIa 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.

RDEA also presented two completed, randomized, double-blind, placebo-controlled, phase I studies 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 IIa 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.

Larger phase IIb is planned

RDEA plans to initiate a comprehensive phase IIb program soon to demonstrate the broad clinical utility of RDEA594 in the treatment of hyperuricemia and gout. Initial results should be available in 4Q09.

An estimated 3-5 million people in the United States -- and approximately 5 million people in the European Union -- suffer from gout, which is the most common form of inflammatory arthritis in men over 40. The incidence and severity of gout is increasing in the United States. There was a 288% increase in gout-related hospitalizations from 1988-2005.

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).