Gout — TMX-67
Gout is a painful condition of the joints, especially affecting the foot, notably the big toe. Deposits of sodium urate crystals build up in the joints, leading to inflammation. Hyperuricaemia is a result of either an increase in the production of uric acid or a decrease in renal uric acid secretion. This is believed to be the major risk factor in the development of gout. Acute attacks are treated with analgesics, but longer term gout treatments centre on reducing serum uric acid levels, either by increasing their excretion, or reducing their formation.
Reducing the formation of uric acid centres on the inhibition of xanthine oxidase/xanthine dehydrogenase inhibitor. Only one such drug, allopurinol, is currently available, and its side-effects include nephropathy, hepatitis and allergic reactions, so further drugs with this action but lower incidences of side-effects would be beneficial.
A new xanthine oxidase inhibitor, TMX-67, is now undergoing development. In vitro studies showed that the compound completely inhibited xanthine oxidase activity in a lung cancer cell line,1 and in vivo studies proved it to be more effective than allopurinol in comparative tests.2,3
The compound is currently undergoing a double-blind, placebo-controlled escalating multiple-dose study to establish its efficacy in human subjects. Doses of 10, 20, 30, 40 and 50mg gave a decrease in mean serum uric acid levels at 24hr of 27, 34, 37, 40 and 47% respectively.4
Phase II trials are now under way at Teijin in Japan, and Phase I studies are being carried out in the US by Teijin's licensee, TAP Pharmaceuticals.