AstraZeneca announces top-line results from phase III monotherapy study of lesinurad in gout patients

AstraZeneca today announced top-line results from LIGHT, a Phase III study investigating the potential of lesinurad as a monotherapy in the small population of gout patients who are intolerant to, or otherwise cannot take, one or both xanthine oxidase inhibitors allopurinol and febuxostat. Lesinurad is an investigational agent being studied as a selective uric acid re-absorption inhibitor (SURI) that inhibits the URAT1 transporter, normalising uric acid excretion and reducing serum uric acid (sUA).

In the trial, lesinurad met the primary endpoint with a statistically significant (p< 0.0001) higher proportion of patients meeting the sUA goal of <6.0 mg/dL at six months compared with those patients treated with placebo.

Patients in the LIGHT study treated with lesinurad monotherapy were more likely to experience serum creatinine elevations and renal adverse events, including serious events, compared to patients on placebo. Other commonly reported adverse events in patients treated with lesinurad monotherapy were diarrhoea, nausea and constipation.

Briggs Morrison, Executive Vice President, Global Medicines Development & Chief Medical Officer said: “The top-line results from LIGHT demonstrate the efficacy of lesinurad monotherapy, while also providing important safety data, in the small population of patients who can’t take xanthine oxidase inhibitors. We await the results of the remaining three Phase III trials that are investigating lesinurad as a combination therapy with xanthine oxidase inhibitors. We believe that combination therapy, addressing both production and excretion of uric acid, may be an effective way to treat gout patients who do not achieve treatment goals on xanthine oxidase inhibitors alone.”

The other Phase III trials in the lesinurad programme are investigating lesinurad in combination with allopurinol in patients not reaching target sUA levels on allopurinol alone (CLEAR1 and CLEAR2) and as a combination therapy with febuxostat in patients with tophaceous gout (CRYSTAL). The results of these studies are expected in mid 2014, and regulatory submissions in the US (NDA) and EU (MAA) are expected in the second half of 2014.

LIGHT (Lesinurad Monotherapy in Gout Subjects Intolerant to Xanthine Oxidase Inhibitors) was a six month study conducted by AstraZeneca and Ardea Biosciences, a wholly-owned subsidiary of AstraZeneca, to assess the sUA lowering effects and safety of 400mg of lesinurad used once daily as a monotherapy compared to placebo in 214 patients with sUA levels ≥ 6.5 mg/dL (highly symptomatic population with mean sUA of 9.3mg/dL at baseline) who are intolerant, or have a contraindication, to allopurinol or febuxostat.