SILVER SPRING, MD. — Members of a Food and Drug Administration advisory panel were divided on whether the approved indication for fenofibric acid, when co-administered with a statin, should be revised based on trial results showing no benefit of the drug in reducing cardiovascular disease risk when added to a statin in patients with type 2 diabetes.
At a meeting May 19, 6 of the 13 members of the FDA’s Endocrinologic and Metabolic Drugs Advisory Committee agreed that the marketing of fenofibric acid should be allowed to continue, with the addition to the label of the main findings of the study – the Action to Control Cardiovascular Risk in Diabetes (ACCORD) Lipid trial. Four panelists, however, voted to recommend that the co-administration indication be withdrawn, citing the lack of solid evidence to support the indication. The remaining three panelists voted to allow continued marketing with no changes to the label.
Fenofibric acid, marketed by Abbott Laboratories as Trilipix, was approved by the FDA in December 2008. The drug’s indication includes its use with a statin as an adjunct to diet to reduce serum triglyceride (TG) levels and increase serum HDL cholesterol levels in patients with mixed dyslipidemia and coronary heart disease (CHD) or a CHD risk equivalent who are on "optimal statin therapy" to achieve their LDL cholesterol goal. Fenofibric acid is the active ingredient of fenofibrate, a fibrate approved in 1993 that is now available in generic formulations.
The FDA convened the panel to review the co-administration indication of fenofibric acid in the context of the ACCORD Lipid study results. That study found no benefit of the combination treatment on major cardiovascular events, compared with treatment with simvastatin alone, over a mean of almost 5 years of follow-up. The study enrolled more than 5,500 patients with type 2 diabetes at high risk of cardiovascular disease, with a range of TG and HDL cholesterol levels. Among women in the study, the rate of major adverse cardiovascular events was higher than that among those on the statin alone. But in another subgroup of patients, those with elevated TG levels (204 mg/dL or higher) and reduced HDL cholesterol levels (34 mg/dL or lower), there was a suggestion of benefit with combination therapy (N. Engl. J. Med. 2010;362:1563-74).
Panelists at the meeting said they were not comfortable drawing any conclusions from analyses of patient subgroups in a negative trial. They voted 13-0 that the FDA should require Abbott to conduct a study to test the hypothesis that add-on therapy with fenofibric acid, compared with placebo, significantly lowers the risk of major adverse cardiovascular events in high-risk patients who have reached their LDL cholesterol goal with a statin but have residual high serum TG and low serum HDL cholesterol levels.
The ACCORD Lipid study was sponsored by the National Heart, Lung and Blood Institute.
The FDA usually follows the recommendations of its advisory panels. Members of FDA advisory panels have been cleared of potential conflicts of interest related to the topic of the meeting; occasionally, they may be given a waiver, but not at this meeting.