Ardea Unveils Positive Results For RDEA594 With Allopurinol Or Febuxostat

Ardea Biosciences (Ardea) has reported additional positive results from a recently completed Phase 2a study of RDEA594, its lead product candidate for the treatment of hyperuricemia and gout.

Additionally, the company has also announced positive results from the second panel of a Phase 1 drug-drug interaction and pharmacodynamic study of RDEA594 in combination with Febuxostat (Uloric, Takeda Pharmaceutical; Adenuric, Ipsen and Menarini).

The combination of RDEA594 and Allopurinol reduced serum urate (sUA) levels an additional 24 percent compared to Allopurinol alone in the second cohort of a Phase 2a proof-of-concept study evaluating the sUA lowering effect, safety and tolerability of combining RDEA594 and Allopurinol in gout patients with hyperuricemia (sUA levels of at least 9mg/dl).

In the study, the response was defined as achieving a target sUA level of less than 6.0mg/dl. Adding 200mg of RDEA594 QD to Allopurinol for an additional week produced a 48% reduction in sUA from baseline with all patients responding. Increasing the dose to 400mg of RDEA594 QD for an additional week resulted in a 54% reduction of sUA from a baseline of 10.2mg/dl to a mean of 4.6mg/dl, which represents a 24% reduction in sUA levels from levels achieved on Allopurinol alone.

Reportedly, all patients responded and 80 percent of patients achieved sUA levels below 5mg/dl. The combination of RDEA594 and Allopurinol was well tolerated and no significant laboratory abnormalities were reported. In the previously reported first cohort of the study, RDEA594 produced significant reductions in sUA levels, was effective in patients with mild to moderate renal impairment, and was well tolerated as a single agent in gout patients with hyperuricemia.

In the second panel of a drug-drug interaction and pharmacodynamic study of RDEA594 with Febuxostat in healthy volunteers, 400mg of RDEA594 QD and 40mg of Febuxostat QD reduced mean sUA levels by 49 and 45%, respectively, when used alone. The combination of RDEA594 with Febuxostat resulted in approximately a 70% mean reduction in sUA levels compared to baseline, with intraday reductions of over 80%, reaching mean sUA levels of 1.2mg/dl.

The combination of RDEA594 and Febuxostat was well tolerated, with Grade 2 elevations of liver enzymes associated with febuxostat treatment as the only significant laboratory abnormalities.

Barry Quart, president and CEO of Ardea, said: “Given its complementary mechanism of action, we believe that RDEA594 is well positioned to meet a significant unmet medical need for patients who do not adequately respond to, or who are intolerant to, currently available gout medications.”