AstraZeneca reported top-line results Friday indicating that its experimental drug lesinurad met the primary endpoint of a Phase III study in patients with gout who are unable to take one or both xanthine oxidase inhibitors allopurinol and febuxostat. The data "demonstrate the efficacy of lesinurad monotherapy, while also providing important safety data, in the small population of patients who cannot take xanthine oxidase inhibitors," commented Briggs Morrison, AstraZeneca's chief medical officer and vice-president of its global medicines development segment.
The LIGHT study consisted of 214 gout patients with serum uric acid (sUA) levels of at least 6.5 mg/dL and who were not suitable for treatment with allopurinol or febuxostat. The patients were randomised to receive AstraZeneca's selective uric acid re-absorption inhibitor or placebo. At six months, results showed a significantly greater proportion of patients achieved sUA levels of less than 6 mg/dL in the lesinurad group than in the placebo group.
However, the company noted that patients given lesinurad were more likely to exhibit elevated serum creatinine levels and adverse renal events, including severe events, than those who received placebo. Deutsche Bank suggested the safety results were a concern, saying that "a clean safety profile is essential for approval and market acceptance" of the drug given that patients with gout often require chronic treatment and may have other health problems.
Morrison said the company is awaiting the results of the remaining three Phase III trials that are investigating lesinurad as a combination therapy with xanthine oxidase inhibitors, adding "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."
AstraZeneca is conducting two late-stage studies, dubbed CLEAR1 and CLEAR2, testing lesinurad in combination with allopurinol in patients who cannot achieve target sUA levels on allopurinol alone. The company is also conducting the CRYSTAL trial of lesinurad in combination with febuxostat for patients with tophaceous gout. Results are expected from these studies in mid-2014, with regulatory filings in the US and EU anticipated in the second half of 2014.