All Trilipix Options Available To Advisory Committee

ACCORD-Lipid trial results could lead members to recommend conducting another trial, revising the label, withdrawing the indication or take no action for Trilipix coadministration with a statin.

FDA is asking an advisory committee to consider the full gamut of options for how to deal with Trilipix and its combination with a statin in the wake of the results of the ACCORD-Lipid trial.

The Endocrinologic and Metabolic Drugs Advisory Committee on May 19 will discuss whether FDA should withdraw approval for coadministration of Abbott's drug with a statin to lower triglyceride levels; continue to allow marketing, but revise the label to incorporate the Action to Control Cardiovascular Risk in Diabetes-Lipid trial findings; or continue marketing with the existing label. The possibility of requiring a clinical trial to test a hypothesis that Trilipix could benefit a sub-group also is up for consideration.

FDA's draft questions posted May 17 split the question, asking the members to vote on the need for another trial and then to vote for status quo, withdrawal or a narrowed indication.

Trilipix (fenofibric acid) is a follow-on to Abbott's TriCor (fenofibrate) and was approved in December 2008, gaining an indication as the only fibrate that could be used with a statin. It also has been approved as monotherapy for a number of conditions.

Most of the options before the panel could lessen the drug's advantage over generic competitors (Also see "Trilipix Use In Diabetics Might Be Restricted After FDA Panel Review Of ACCORD Data" - Pink Sheet, 25 Apr, 2011.).

ACCORD Efficacy And Trilipix Safety To Be Evaluated

The government-funded ACCORD trial studied whether adding fibrate to simvastatin therapy in patients with type 2 diabetes would reduce the rate of cardiovascular disease events in high-risk patients compared to simvastatin monotherapy.

The results, released in March 2010, showed no difference in CV outcomes. They also suggested the therapy may only be appropriate for a minority of diabetes patients (Also see "Abbott's Fibrate Franchise Will Likely Remain Limited To High-Risk Patients After ACCORD" - Pink Sheet, 14 Mar, 2010.).

Abbott has already been set back on one product by ACCORD: the fixed-dose combination of Trilipix and AstraZeneca's Crestor (rosuvastatin) received a "complete response" letter in March 2010 (Also see "Abbott/AstraZeneca's Certriad Bounced By FDA; ACCORD May Be The Culprit" - Pink Sheet, 30 Mar, 2010.).

The committee is being asked to interpret the primary efficacy results of ACCORD-Lipid in relation to Trilipix's coadministration indication.

Sub-Group Success And Failure?

FDA did identify one group that may benefit from fenofibrate plus statin therapy: patients with high triglyceride levels (>204 mg/dL in the trial) and low high-density lipoprotein cholesterol (<34 mg/dL). A pre-specified sub-group analysis showed 12.4% of patients in the group on fenofibrate plus simvastatin had major adverse cardiac events, versus 17.3% on simvastatin monotherapy.

Abbott seems prepared for the indication to be limited. In its briefing document, the company maintains the data show coadministration of Trilipix and a statin has a favorable benefit-risk profile in that group. The combination "remains an important therapeutic option for appropriately selected patients," the company says.

Advisory committee members also will be asked to give their interpretation of the sub-group analysis and how it relates to use of Trilipix plus statin therapy.

In addition, the committee will be asked for its opinion of the study's finding that women receiving fenofibrate plus simvastatin had a higher MACE incidence rate (9.1%) than those only on a simvastatin (6.6%). The clinical significance of the finding is unclear, FDA said in a Federal Register notice announcing the advisory committee meeting.

FDA admitted there remain several questions about fibrates and suggested another study could provide more answers about performance, especially within the sub-groups.

"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," the agency's briefing material states. "Such a trial would also provide additional information regarding the cardiovascular effects of fenofibrate plus statin versus statin monotherapy in women versus men."

-Derrick Gingery ([email protected])