AstraZeneca has announced positive subanalysis data of the Phase III lesinurad studies (CLEAR1, CLEAR2 and CRYSTAL) for the treatment of hyperuricemia associated with gout, in combination with a xanthine oxidase inhibitor (XOI).The results demonstrated a consistent efficacy and safety profile in patients with normal renal function, as well as patients with mild to moderate renal impairment. This subanalysis was presented at the American College of Rheumatology (ACR) 2015 Annual Meeting in San Francisco, California.
"As renal impairment and gout frequently co-exist we felt it was important to investigate the benefit and risk profile of lesinurad in patients with varying degrees of renal function," said Chris Storgard, MD, Vice President, Clinical Research and Development, Ardea Biosciences, a member of the AstraZeneca Group. "These key findings showed that lesinurad, in combination with the current standard of care of XOIs, effectively lowered serum uric acid (sUA) and enabled more gout patients with mild or moderate renal impairment to achieve the recommended sUA treatment goals."
In CLEAR1, CLEAR2 (full study results here) and CRYSTAL (full study results here) efficacy and safety endpoints from these pivotal Phase III trials were analyzed in patients with normal renal function (eCrCl ≥90 mL/min), patients with mild or moderate renal impairment (<90 ml/min) and specifically those with moderate renal impairment (<60 ml/min). Patients with severe renal impairment (<30 ml/min) were not studied. Lesinurad 200 mg in combination with an XOI resulted in consistent efficacy with a similar proportion of patients achieving sUA targets across these renal function categories. In addition, safety findings were consistent between treatment groups across all renal function categories.
Renal related adverse events increased with decreasing renal function irrespective of lesinurad treatment, with no notable treatment group differences within renal function categories. The incidence of serum creatinine (sCR) elevations was dose dependent but did not increase with decreasing renal function. Renal function (eCrCl) was stable over time in all treatment groups and across all renal function categories.
Last month, the U.S. Food and Drug Administration's Arthritis Advisory Committee voted 10 to 4 to recommend the approval of lesinurad 200 mg for the treatment of hyperuricemia associated with gout, in combination with a xanthine oxidase inhibitor (XOI).
The Prescription Drug User Fee Act (PDUFA) target goal date for lesinurad is December 29, 2015.
Lesinurad is also under regulatory review in the European Union and other territories.
Gout is a serious and debilitating form of inflammatory arthritis caused by hyperuricemia (elevated sUA). Gout affects millions of Americans, many of whom do not reach recommended sUA treatment goals on XOIs which decrease production of uric acid. For those inadequately controlled patients, the addition of a urate-lowering therapy to increase excretion of uric acid, may help them achieve treatment goals.