AstraZeneca's acquisition of Ardea Biosciences in mid-April for US$1.26 billion reflects growing interest in the gout space: Ardea's lead candidate is lesinurad, which is in Phase III trials for the reduction of hyperuricaemia in gout. Takeda, too, has been building up its gout franchise, most recently with the $800 million acquisition in April of URL Pharma, which markets the only approved version of colchicine in the United States. For a disease that has only seen two new drugs reach the market in nearly four decades, the current pipeline--with one drug under US Food and Drug Administration (FDA) review and at least five drugs in Phase II or III trials --is experiencing a surge.
The increased interest has been driven in part by the recent realization that allopurinol, a mainstay treatment since the mid-1960s, leaves a significant unmet medical need. At the same time, renewed academic interest in gout over the past decade has led to new insights into the biology and epidemiology of the disease. So although allopurinol's affordability and clinical track record will make it tough for new drugs to become first-line therapies, companies are nevertheless betting big that there is space in the market for additional therapeutic options.
Gout--which is estimated to affect at least 15 million patients worldwide--is an arthritic inflammatory disease that results from excess serum levels of uric acid, an end product of purine metabolism. Serum uric acid levels that rise above the solubility point of 6 mg per dl cause hyperuricaemia, a condition in which monosodium urate crystals can form in joints and other tissues and cause painful inflammatory flares.
Clinicians have two complementary therapeutic approaches: they can use uric acid-lowering drugs to treat the underlying disease and anti-inflammatory medicines to prevent or reduce the pain of flare-ups. The mainstay of uric acid-lowering treatment is allopurinol, a drug that was approved by the FDA in 1966. Allopurinol blocks xanthine oxidase, which catalyses the last two steps of uric acid synthesis, resulting in lower serum levels of uric acid. Once serum levels drop below 6 mg per dl, monosodium urate crystals resolubilize to reverse the disease course.
Although two additional uric acid-lowering drugs have been...