Arthritis Advisory Committee votes in favor of lesinurad in combo with xanthine oxidase inhibitor for gout

Despite airing numerous concerns related to safety and the degree of efficacy, members of the FDA’s Arthritis Advisory Committee voted positively today for the recommendation of lesinurad oral tablets in combination with a xanthine oxidase inhibitor for the treatment of hyperuricemia associated with gout.

The 10-to-4 vote in favor of the recommendation followed a discussion about renal and cardiovascular events, and what some perceived as a minimal efficacy profile.

“Just to clarify – those of you who voted ‘no’ for safety and ‘yes’ for the efficacy – what I am hearing you say is that – looking at the overall risk-to-benefit – there is going to be more potential for benefit than harm. Is that correct?” Tuhina Neogi, MD, PhD, acting chairperson of the Arthritis Advisory Committee, asked members, who responded affirmatively.

Numerous committee members cited unmet needs and a lack of other options for patients with gout as primary reasons for casting a favorable vote. However, several members said they were conflicted about the decision, and noted safety concerns related to renal and cardiovascular adverse events during the four trials, particularly with 400-mg dose or higher. Other concerns included the size of the study population, the duration of studies and a change in trial protocols to require at least 2 L daily hydration by patients in the studies after renal events were observed, and whether patients would adhere to those requirements in a larger population.

Further recommendations included detailed labeling with contraindications and potential adverse events, a standard minimum patient creatinine clearance threshold, a clear monitoring protocol and detailed analysis of further studies to determine which patients may be at highest risk for adverse events or who may benefit the most from treatment.

Other suggestions included a study protocol for a twice-daily dose regimen, exploration of comorbidities in further studies and long-term studies to confirm the expected increased efficacy of urate-lowering treatment over time compared with what some members described as low during the 1-year study period. – by Shirley Pulawski

Reference: www.fda.gov