Lesinurad for treatment of hyperuricemia associated with gout, in combination with a xanthine oxidase inhibitor
The US Food and Drug Administration’s ( FDA ) Arthritis Advisory Committee ( AAC ) voted 10 to 4 to recommend the approval of Lesinurad 200mg tablets for the treatment of hyperuricemia associated with gout, in combination with a xanthine oxidase inhibitor ( XOI ).
The AAC reviewed safety and efficacy data from the pivotal phase III combination therapy programme trials, representing the largest clinical trial data set of gout patients treated with combination urate lowering therapy.
Lesinurad is the first selective uric acid reabsorption inhibitor, or SURI, in the US. It inhibits the urate transporter, URAT1, which is responsible for the majority of the renal reabsorption of uric acid.
Lesinurad also inhibits organic anion transporter ( OAT4 ) a uric acid transporter involved in diuretic-induced hyperuricemia. In addition, in patients, Lesinurad does not inhibit OAT1 and OAT3, which are drug transporters in the kidney associated with drug-drug interactions.
The goal of serum uric acid lowering treatment is to reduce serum uric acid levels to the target level of less than 6.0mg/dL ( 360 mcmol/L ) as recommended by both the American College of Rheumatology ( ACR ) and the European League Against Rheumatism ( EULAR ).
To improve signs and symptoms such as tophaceous gout, the ACR guidelines state that achieving and maintaining serum uric acid levels less than 5.0 mg/dL ( 300 mcmol/L ) may be required.
Among patients treated in clinical trials, less than 50% of patients on Allopurinol 300 mg reached serum uric acid target levels less than 6.0mg/dL ( 360 mcmol/L ).
Gout is a serious and debilitating form of inflammatory arthritis caused by hyperuricemia. Many patients do not reach recommended serum uric acid treatment goals on the current standard of care ( XOIs ), which decrease production of uric acid. Elevated serum uric acid leads to the deposition of crystals primarily in the joints and in other tissues. This can result in recurrent attacks of inflammatory arthritis and, if left uncontrolled, could lead to chronic, progressive arthritis, and tophus ( visible deposits of urate crystals ).
For inadequately controlled patients, the addition of a urate lowering therapy to increase excretion of uric acid, may help patients achieve treatment goals. ( Xagena )
Source: AstraZeneca, 2015