Ardea Biosciences, Inc. (Nasdaq: RDEA) 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®, Takeda Pharmaceutical Company Limited; Adenuric®, Ipsen), are being presented 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 ≥ 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 ≥ 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.”