FDA Questions Safety and Dosing of AZ’s Investigational Gout Treatment

FDA reviewers are questioning the safety and dosing of AztraZeneca’s investigational gout treatment lesinurad and whether a risk evaluation and mitigation strategy would suffice to address those concerns.

According to background materials released by the agency, four phase 3 trials found both 200 mg and 400 mg formulations of the medication lowered serum uric acid levels in the majority of patients compared with placebo. But lesinurad, especially in the larger once-daily dose, was also linked to a high number of serious adverse events, including heart and kidney problems.

Patients on the 200 mg dose also suffered side effects, but not as serious ones, suggesting toxicity with lesinurad is dose-dependent, the FDA says, raising the question of “whether a lower nominal dose given twice daily may have provided similar efficacy with a better safety profile.”

The FDA’s Arthritis Advisory Committee met last to discuss AZ’s NDA for the drug, which, if approved, would be only the second new treatment for gout since allopurinol was approved 49 years ago. The other, Takeda and Ipsen Pharmaceuticals’ Uloric (febuxostat), approved in 2009, also carries cardiovascular risks and doesn’t help every patient.

AZ acquired lesinurad when it purchased San Diego-based Ardea Biosciences in 2012 and hoped it would reap benefits in the growing gout market, which affects about 8.3 million people in the U.S. each year. — Victoria Pelham