AstraZeneca has reported positive top-line results from three pivotal Phase III clinical trials evaluating the potential of lesinurad, a selective uric acid re-absorption inhibitor (SURI), as a combination therapy to treat people with symptomatic gout.
The three Phase III trials include CLEAR1, CLEAR2 and CRYSTAL, which were conducted by the company’s subsidiary Ardea Biosciences.
The CLEAR1 and CLEAR2 trials assessed lesinurad 200mg and 400mg once daily in combination with the xanthine oxidase (XO) inhibitor allopurinol, in symptomatic gout patients not achieving target sUA levels on their current allopurinol dose.
The CRYSTAL trial evaluated lesinurad 200mg and 400mg once daily in combination with the XO inhibitor febuxostat 80mg once daily in gout patients with tophi.
In the CLEAR1 and CLEAR2 trials, both lesinurad 200mg and 400mg in combination with allopurinol met the primary endpoint, while in the CRYSTAL trial the combination of lesinurad 400mg and febuxostat met the primary endpoint.
The company said that lesinurad 200mg did not achieve statistical significance at month six but its combination with febuxostat was superior compared with placebo plus febuxostat at all other time points.
AstraZeneca Global Medicines Development executive vice-president and chief medical officer Dr Briggs Morrison said: "Gout is a serious, chronic and debilitating inflammatory disease.
"There is a significant unmet need, with 40% to 70% of gout patients not reaching target levels of serum uric acid with the current standard of care.
"We are encouraged by our initial review of the top-line results from the CLEAR1, CLEAR2 and CRYSTAL studies, which provide important new information on the efficacy and safety of lesinurad in combination with febuxostat and allopurinol.
"These data indicate that combination therapy with lesinurad may be a potential treatment option for gout patients."
Upper respiratory tract infection, nasopharyngitis and back pain are the three most commonly reported adverse events observed in the CLEAR1 and CLEAR2 trials for patients receiving lesinurad in combination with allopurinol.
The three most commonly reported adverse events seen in the CRYSTAL trial for patients receiving lesinurad in combination with febuxostat were nasopharyngitis, arthralgia and upper respiratory tract infection.
Image: Gout presenting in the metatarsal-phalangeal joint of the big toe: note the slight redness of the skin overlying the joint. Photo: courtesy of James Heilman MD.