FDA reviewers raise doubts about AstraZeneca's $1.3B gout drug

AstraZeneca's ($AZN) new gout therapy, acquired in a $1.3 billion buyout, might not be effective enough to outweigh its safety risks, according to FDA staff, casting doubts on the drug's future as it heads for a key panel vote.

In briefing documents released ahead of an FDA committee meeting, agency reviewers noted that AstraZeneca's lesinurad successfully lowered gout-worsening uric acid gout in its clinical trials, but not without alarming spikes in kidney side effects and cardiovascular issues. The FDA's independent committee on arthritis drugs is slated to review AstraZeneca's application on Friday, voting whether to recommend approval for lesinurad.

The drug, picked up in AstraZeneca's 2013 acquisition of Ardea Biosciences, is a selective uric acid reabsorption inhibitor that blocks the URAT1 transporter, treating gout by normalizing acid excretion and reducing serum levels, or sUA.

In Phase III trials, AstraZeneca tested two doses of lesinurad--200 mg and 400 mg--alongside standard therapy. The larger dose led to significant reductions in sUA, but not without marked increases in renal adverse events--many of which were serious--and spikes in cardiovascular risks, the FDA said. The 200-mg dose was better tolerated, according reviewers, but didn't perform as well on its efficacy goals, getting 30% more patients to target sUA levels in two trials but missing statistical significance in a third.

On Friday, panelists will weigh in on whether 200 mg of lesinurad merits approval anyway. The FDA is not required to follow the advice of its committees, but it commonly does.

- read the briefing (PDF)