On January 11th, 2019, Takeda Pharmaceuticals appeared before a joint session of the Arthritis Advisory and the Drug Safety and Risk Management Advisory Committees. They were seeking approval for their supplemental new drug application for Uloric tablets (sNDA 021-856).

Uloric, a xanthine oxidase inhibitor indicated for the chronic management of hyperuricemia in patients with gout, was FDA-approved in 2009. Prior to this approval, Uloric was rejected twice due to concerns about cardiovascular safety that arose during clinical trials.

As a stipulation of the 2009 approval, the FDA requested an extensive post-marketing safety trial to evaluate the cardiovascular safety which was the subject of this committee meeting. The study is entitled Cardiovascular Safety of Febuxostat and Allopurinol in Patients with Gout and Cardiovascular Morbidities (CARES).

In this meeting, there were four discussion questions and one voting questions. The vote addressed whether a patient population exists in which the benefit-risk profile for Uloric is favorable for the treatment of hyperuricemia in patients with gout. It resulted in 19 YES, 2 NO, and 1 ABSTENTION.

The majority of the committee members felt that the benefit/risk ratio was favorable for the treatment of hyperuricemia in patients with gout. However, they also suggested stronger risk labeling, a boxed warning, a second-line therapy indication, an update to the gout treatment guidelines by the American College of Rheumatology (ACR), and “Dear Healthcare Provider” letters to communicate the risk to patients and their providers so they can make an informed decision on a care plan. One committee member disagreed with the approval and expressed concerns that the drug causes death in some patients.

The agency is not obligated to follow its panel’s recommendation, but normally does so.

Following the recommendations by the joint committee, on February 21, 2019 the FDA updated the prescribing information to require a Boxed Waring and a new patient Medication Guide. In addition, they limited the approved uses of Uloric to patients who are not treated effectively or experience severe side effects with allopurinol.

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