May 17th, 2011

FDA Reviewers Scrutinize ACCORD and Trilipix

The FDA has released the agenda, questions, roster, and briefing materials for Thursday’s meeting of the Endocrinologic and Metabolic Drugs Advisory Committee in which the ACCORD trial and the fate of Abbott’s Trilipix (fenofibric acid) will be discussed.

The key questions on which the advisory committee members will be asked to vote are:

  • Should the FDA require a new clinical trial to demonstrate the benefit of Trilipix in high-risk patients?
  • Regarding Trlipix’s indication for coadminstration with a statin: Should the current indication be maintained, withdrawn, or revised to incorporate the findings from ACCORD?

The FDA reviewers were critical of the data in support of fibrate therapy. Here is the conclusion of the main review of ACCORD:

Fibrates have been investigated in at least five major clinical trials and have produced mixed results. Although outcome trials with gemfibrozil have shown cardiovascular benefit over placebo, fenofibrate has not. The answer to the question of why fenofibrate produced unimpressive cardiovascular outcome results relative to gemfibrozil is not known. The inconsistent findings may be a result of pharmacodynamic differences between individual fibrates and diverse study populations or both.

One way to obtain a more definitive answer to the question of fenofibrate’s cardiovascular benefit when added to a statin is to conduct a clinical trial specifically designed to test the hypothesis that, in high-risk men and women at LDL-C goal on a statin with residually high TG and low HDL-C, treatment with fenofibrate versus placebo significantly reduces the risk for major adverse cardiovascular events (MACE). Such a trial would also provide additional information regarding the cardiovascular effects of fenofibrate plus statin versus statin monotherapy in women versus men.

The FDA also said that postmarketing observational safety studies had found a moderate to large relative increase in rhabdomyolysis with statins plus fibrates compared with statin monotherapy, but that the absolute increase was still small.

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