Ardea Biosciences, Inc. Announces Positive Results for RDEA594 in Combination with Febuxostat or Allopurinol in Gout Patients

SAN DIEGO, Nov. 8, 2010 /PRNewswire-FirstCall/ -- Ardea Biosciences, Inc. (Nasdaq: RDEA) today announced positive results from two clinical studies of RDEA594 in combination with currently marketed drugs for the treatment of gout patients, febuxostat (Uloric®) and allopurinol. RDEA594, Ardea’s lead product candidate for the chronic management of hyperuricemia and gout, is an orally administered compound that inhibits the URAT1 transporter, a biological mechanism that is different from, but complementary to, that of allopurinol and febuxostat. While allopurinol and febuxostat account for greater than ninety percent of U.S. prescriptions for the chronic treatment of gout, approximately one half of patients do not adequately respond to standard doses of these drugs, leaving a significant portion of the gout population with limited options.

Combination of RDEA594 and Febuxostat (Study 111)

In this 21-patient, open-label, clinical pharmacology study, 100 percent of patients receiving the combination of RDEA594 and febuxostat achieved serum urate (or “sUA”) levels below the clinically important target of 6 mg/dL, compared to 67 percent and 56 percent for 40 mg and 80 mg, respectively, of febuxostat alone. At the highest combination doses tested (600 mg of RDEA594 and 80 mg of febuxostat), 100 percent of patients also reached sUA levels below 4 mg/dL, with 58 percent achieving levels below 3 mg/dL. No patient achieved these reduced sUA levels on either dose of febuxostat alone. The study included 2 cohorts of gout patients with sUA greater than 8 mg/dL on no urate-lowering therapy. All patients received colchicine beginning one week prior to baseline and continuing for 5 weeks for flare prophylaxis. The first cohort of patients in the study consisted of 12 gout patients with a median baseline sUA of 9.2 mg/dL who were administered 40 mg febuxostat for the first week, 40 mg febuxostat in combination with 400 mg RDEA594 for the second week, and then 40 mg febuxostat in combination with 600 mg RDEA594 for the third week. This sequence was repeated with 80 mg febuxostat in a second cohort of 9 patients who had a median baseline sUA of 10.4 mg/dL.

The combination of RDEA594 and febuxostat was synergistic, with the addition of 600 mg RDEA594 producing additional 39 and 51 percent reductions compared to 40 mg and 80 mg febuxostat alone, respectively. At the highest combination doses in cohorts one and two, patients achieved intraday median sUA levels of 2.4 mg/dL and 2.0 mg/ dL, respectively. These levels of sUA reduction suggest the combination of RDEA594 and febuxostat may be particularly useful in patients who have accumulated large deposits of uric acid, or tophi. In these patients, the substantial reduction of sUA, coupled with increased excretion of uric acid associated with RDEA594’s URAT1 mechanism, may lead to improved resolution of these tophi.

No clinically relevant drug interactions were observed between RDEA594 and febuxostat. The combination of RDEA594 and febuxostat was well tolerated, with no serious adverse events or discontinuations due to adverse events. There were no Grade 2 or higher increases in serum creatinine on RDEA594 alone or the combination with febuxostat, but one Grade 2 serum creatinine increase occurred on colchicine alone. There was one Grade 3 increase in the liver enzyme, alanine aminotransferase (ALT), on febuxostat 40 mg alone, which normalized during combination treatment with RDEA594.

Combination of RDEA594 and Allopurinol (Study 110)

In this 20-patient, open-label clinical pharmacology study, 100 percent of patients receiving all combinations of RDEA594 and allopurinol achieved sUA reductions to below the 6 mg/dL target. On 300 mg allopurinol alone, only 20 percent of patients achieved target sUA levels below 6 mg/dL. On 600 mg RDEA594 alone, 67 percent of patients achieved sUA levels below 6 mg/dL, which was significantly better than allopurinol alone (p < 0.05). At the highest combination doses tested, 90 percent of patients also reached sUA levels below 5 mg/dL, and 50 percent reached levels below 4 mg/dL. Study 110’s design was similar, but not identical, to Study 111 and included 2 cohorts of gout patients with sUA greater than 8 mg/dL on no urate-lowering therapy who began colchicine dosing one week prior to baseline and continued it for 5 weeks. In this study, the first cohort of 10 patients with a median baseline sUA of 9.8 mg/dL received 300 mg allopurinol alone for the first week, then 300 mg allopurinol plus 400 mg RDEA594 for the second week, followed by 400 mg RDEA594 alone for the third week. In the second cohort, 10 patients with a median baseline sUA of 9.1 mg/dL followed the same dosing scheme for the same time period at a dose of 300 mg allopurinol and 600 mg RDEA594.