FDA committee to review fate of Abbott's cholesterol drug

FDA’s Endocrinologic & Metabolic Drugs Advisory Committee is meeting today to discuss whether previous indications for Abbott Laboratories fenofibrate (Trilipix) should be reduced after results of the ACCORD-Lipid trial showed that the addition to a statin to fenofibrate did not significantly reduce major adverse cardiac event rates in diabetic patients.

In 2008, the FDA approved Abbot’s cholesterol drug fenofibrate and has indicated the drug to be used in combination with a statin and to reduce elevated LDL-cholesterol, total cholesterol, triglycerides and apolipoprotein B. In addition, the drug is indicated to help increase HDL-cholesterol levels in patients with lipid problems. The drug is also approved as a monotherapy to reduce triglycerides (TG) in severe hypertriglyceridemia patients.

“Fibrates have been investigated in at least five major clinical trials and have produced mixed results,” the FDA briefing materials stated.

For example, the ACCORD-Lipid (Action to Control Cardiovascular Risk in Diabetes – Lipid) trial enrolled 5,518 diabetic patients who were randomized to receive either simvastatin (Zocor, Merck) plus fenofibrate (2,765 patients) or simvastatin plus placebo (2,753 patients). The researchers used MACE rates as the study’s primary outcome. After an average 4.7-year follow-up, the researchers reported that MACE rates for the statin plus placebo group were 11.3 percent compared to the 10.5 percent in the statin plus fenofibrate group.

Likewise, the previous FIELD trial showed no significantly cardiovascular benefit when use of the drug was compared to placebo.

On March 15, 2010, the FDA issued a statement to health professionals saying that the agency was aware of the ACCORD-Lipid trial and its results and that they would review and re-evaluate the data.

During the May 19 meeting, FDA members will discuss:

• Primary results from the ACCORD-Lipid trial as they relate to fenofibrate’s indication to be co-administered with a statin;
• Subgroup findings that MACE rates in women randomized to receive statin plus placebo were 6.6 percent compared to 9.1 percent in women randomized to statin plus fenofibrate;
• Subgroup findings of patients with TG levels greater than or equal to 204 mg/dl and HDL-C levels that were greater than or equal to 34 mg/dl. Researchers found MACE rates for these patients to be 17.3 percent in those administered statin plus placebo and 12.4 percent in those randomized to receive simvastatin plus fenofibrate;
• Safety profiles of fenofibrate;
• Risk-benefit profiles of fenofibrate when used in combination with a statin; and

• The recommended actions of the FDA regarding fenofibrate’s indication to be used with a statin: Allow continued marketing, withdraw approval for fenofibrate’s indication for coadministration with a statin, allow marketing of the drug with a statin but revise labeling or require a clinical trial to be conducted to evaluate that in high-risk patients at LDL-C goals on a statin with high TG and low HDL-C, add-on therapy with fenofibrate vs. placebo lowers MACE rates.

During the meeting Abbott will make the case that fenofibrate when administered in combination with a statin “continues to have a favorable benefit-risk profile in patients with elevated triglycerides and/or low high-density lipoprotein cholesterol.”

The company said that the results of the ACCORD Lipid trial confirm the results of four prior trials: Helsinki Heart Study (HHS, published in 1987), the Veterans Affairs High-Density Lipoprotein Intervention Trial (VA-HIT, published in 1999), the Bezafibrate Infarction Prevention trial (BIP, published in 2000) and the Fenofibrate Intervention and Event Lowering in Diabetes trial (FIELD, published in 2005).

The meeting will adjourn today at 5 p.m. and the roster will include 13 voting members (five committee members and eight temporary members).