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FDA Panel to Tackle Febuxostat’s CV Safety

The spotlight is on Takeda’s urate-lowering drug febuxostat (Uloric) and its safety this Friday when a panel of FDA advisors convenes to discuss potential regulatory action regarding cardiovascular risk of this gout medicine. Febuxostat is currently indicated for the chronic management of hyperuricemia in patients with gout.

Panel members will discuss the results from the FDA-required postmarketing safety trial called CARES. Last March, that trial found febuxostat was inexplicably linked to more cardiac deaths than was allopurinol, the mainstay in patients with gout and cardiovascular disease.

Arthritis Advisory Committee and the Drug Safety and Risk Management Advisory Committee panelists will discuss the potential biological mechanisms behind cardiovascular events in febuxostat use and the strength of the safety signal, weighing the benefits and risks of the drug for patients with gout.

Direction will also be given for potential regulatory activities — such as withdrawal of febuxostat from the market or limiting its use to patients who have failed allopurinol therapy.

One specialist (not on the advisory committee) was Daniel Arkfeld, MD, of the University of Southern California Keck School of Medicine in Los Angeles. He told MedPage Today that there are few alternatives, especially in renal patients with high creatinine in whom allopurinol is “more dangerous due to hypersensitivity reactions as well.”

A black box warning might be a good option if febuxostat were to stay, Arkfeld suggested.

FDA twice rejected the new drug application for febuxostat (in 2005 and 2006) because of concerns over cardiovascular risk. Approval in 2009 came on the condition that a postmarketing safety study be conducted and that the drug label warn of a higher rate of cardiovascular thromboembolic events with the drug.

A safety communication from the agency was released in November 2017 based on a preliminary analysis of CARES. Public Citizen petitioned in June 2018 for the drug to be pulled altogether.