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FDA Approves Zurampic for Hyperuricemia
The FDA has approved lesinurad (Zurampic, AstraZeneca) to be used in combination with a xanthine oxidase inhibitor (XOI) to treat high hyperuricemia. The drug works by aiding the kidneys in the excretion of uric acid by inhibiting transporter proteins involved in uric acid reabsorption.
In combination with the current standard of care, XOIs allopurinol or febuxostat, lesinurad provides a dual mechanism of action to increase excretion and decrease production of uric acid, enabling more patients with inadequately controlled gout to achieve target treatment goals.
The FDA approval is based on data from three pivotal phase III studies, CLEAR1, CLEAR2, and CRYSTAL, which represent the largest clinical trial data set of gout patients (n = 1,537 total) treated with combination urate-lowering therapy.
CLEAR1 and CLEAR2 evaluated the efficacy and safety of a once-daily dose of Zurampic in combination with allopurinol compared to allopurinol alone. In these two studies, lesinurad in combination with allopurinol met the primary endpoint, with approximately twice as many patients achieving the serum uric acid (sUA) goal of less than 6.0 mg/dL (360 mcmol/L) by month 6, compared to those treated with allopurinol alone.
CRYSTAL evaluated the efficacy and safety of a once-daily dose of lesinurad in combination with febuxostat 80 mg compared to febuxostat 80 mg alone in gout patients with tophi (visible deposits of urate crystals in joints and skin). Patients were administered febuxostat 80 mg orally once daily for three weeks before randomization. In CRYSTAL, results showed Zurampic 200 mg in combination with febuxostat demonstrated greater (nominal P < 0.05) sUA lowering to the target for tophaceous gout of less than 5.0 mg/dL (300 mcmol/L) compared to febuxostat alone at all months except at the time of the primary endpoint, month 6 (56.6% versus 46.8%, nonsignificant). In the subgroup of patients with baseline sUA of at least 5.0 mg/dL (300 mcmol/L) (i.e., those above the recommended sUA treatment target for tophaceous gout on febuxostat alone), lesinurad 200 mg in combination with febuxostat resulted in more subjects reaching the target sUA of less than 5.0 mg/dL (300 mcmol/L) compared to febuxostat alone at month 6.
In a pooled analysis of the three clinical trials, the safety profile was similar for lesinurad 200 mg in combination with an XOI to that of an XOI alone, with the exception of an increased incidence of predominantly reversible serum creatinine elevations.
Source: AstraZeneca, December 22, 2015.