Metabolex today announced positive results from its clinical study of arhalofenate in combination with febuxostat (Uloric™, Takeda Pharmaceutical Company Limited). A key goal in the treatment of gout is to address the patient's underlying hyperuricemia by treatment with drugs that lower serum uric acid (sUA). In the US, the goal of treatment is to reduce sUA levels to below 6 mg/dL. However, patients with severe tophaceous gout would benefit from reducing their sUA values below 5 or even 4 mg/dL because this would result in more rapid dissolution of their UA crystal deposits. Most patients treated with currently marketed xanthine oxidase inhibitors (allopurinol or febuxostat) alone do not reach these goals. Arhalofenate, Metabolex's lead product candidate for the treatment of hyperuricemia and gout, is a uricosuric agent that could provide additional sUA lowering when used in combination with xanthine oxidase inhibitors and be a treatment option for patients with tophaceous gout.
Clinical Study of Combination of Arhalofenate and Febuxostat
This study was an open label clinical pharmacology study on a single cohort of 11 gout patients with sUA levels of at least 8 mg/dL (mean of 9.1 mg/dL). The primary goal of the study was to assess the response rate (percentage of patients reaching goal) for the sUA targets of 5 and 4 mg/dL when treated in combination with the highest dose (80 mg) of febuxostat approved in the US and two doses (400 and 600 mg) of arhalofenate. The patients were either treatment naive or had discontinued uric acid lowering therapies for a period prior to entering the study. All patients received colchicine throughout the study for flare prophylaxis. After a two week run-in period for sUA stabilization, all 11 patients received febuxostat (80 mg) for one week. Subsequently, patients were administered 400 mg of arhalofenate for two weeks followed by up-titration of arhalofenate to 600 mg for an additional two weeks. All patients were followed for an additional two weeks.