AstraZeneca on Wednesday announced positive top-line results from three placebo-controlled Phase III trials evaluating the experimental selective uric acid re-absorption inhibitor lesinurad as a combination therapy for patients with symptomatic gout. Chief medical officer Briggs Morrison noted that between 40 percent and 70 percent of gout patients are "not reaching target levels of serum uric acid (sUA) with the current standard of care," adding the data suggest "combination therapy with lesinurad may be a potential treatment option."
The CLEAR1 and CLEAR2 trials involved 603 and 610 gout patients, respectively, who failed to achieve target sUA levels and experienced at least two gout flares in the preceding 12 months. Participants were randomised to receive one of two doses of lesinurad added to the xanthine oxidase (XO) inhibitor allopurinol, or allopurinol alone. Study results illustrated that a significantly higher proportion of patients in both combination arms achieved the sUA target of less than 6 mg/dL at six months, versus the allopurinol-alone group.
In the CRYSTAL study, 324 patients with tophaceous gout were randomly assigned one of two doses of lesinurad plus the XO inhibitor febuxostat, or febuxostat alone. For the higher lesinurad dose, the combined therapy was associated with a significantly greater proportion of patients who achieved sUA levels of less than 5 mg/dL at all time points, versus febuxostat alone. Meanwhile, the combination treatment featuring the lower dose of lesinurad was linked to a greater proportion of patients reaching the sUA target at all time points excluding the six-month measurement.
The most common adverse events for the combination therapy in the CLEAR1 and CLEAR2 trials were upper respiratory tract infection, nasopharyngitis and back pain, whereas in the CRYSTAL study they were nasopharyngitis, arthralgia and upper respiratory tract infection. AstraZeneca also stated that a greater incidence of renal-related adverse events and kidney stones was observed in patients administered the higher lesinurad dose, while no difference was found for the lower dose. The company noted that a complete safety and tolerability assessment for the three studies is ongoing, and that full results will be presented at a scientific meeting later this year.
In December, AstraZeneca reported top-line results from the 214-patient LIGHT study demonstrating that lesinurad was associated with a significantly greater likelihood of achieving sUA levels of less than 6 mg/dL, compared with placebo, among patients with gout who were unsuitable for XO inhibitor therapy.
The drugmaker noted that it is proceeding with the preparation of regulatory submissions for lesinurad, acquired in its 2012 purchase of Ardea Biosciences, as a combination therapy. Although analysts estimate the drug could generate $281 million in sales by 2019, if approved, Deutsche Bank analyst Mark Clark suggested the drug's safety profile could limit its uptake, adding that a clean safety profile may be critical for regulatory clearance.
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