FDA Drug Safety Communication

Review update of Trilipix (fenofibric acid) and the

ACCORD Lipid trial

Nicolas BERNARDFlorent ZOONEKYND December 2nd,2011

Introduction

http://www.fda.gov/downloads/AdvisoryCommittees/CommitteesMeetingMaterials/Drugs/EndocrinologicandMetabolicDrugsAdvisoryCommittee/UCM258120.pdf

Action of Fenofibrate

Action via PPARα : Increase lipoprotein liposis Stimulation of β-oxydation Increase removal of LDL

particules Increase HDL production

Pharmacological consequences : Reduce TG Increase HDL-C Variable effects on LDL-C

ACCORD Trial ACCORD = Action to Control Cardiovascular Risk in

Diabetes Study began in 2001 and took place in 77 clinical sites

across United States and Canada. Three clinical trials, which tested different treatment

approaches to determine the best ways to decrease the high rate of major CVD events in patients with type 2 diabetes :

• ACCORD blood sugar trials• ACCORD blood pressure trials• ACCORD lipids trials

http://www.nhlbi.nih.gov/health/prof/heart/other/accord/q_a.htm#questions

Fenofibrate + simvastatin VS simvastatin + placebo 5518 patients with modest degree of dyslipidemia(2765

randomized to fenofibrate) Primary Outcome: First occurrence of a major

cardiovascular event (nonfatal MI, nonfatal stroke, cardiovascular death)

Mean duration of follow up was 4.7 years

ACCORD Lipid Trial

Primary Outcome

http://www.nejm.org/doi/full/10.1056/NEJMoa1001282#t=articleResults

Primary Outcome

http://www.fda.gov/downloads/AdvisoryCommittees/CommitteesMeetingMaterials/Drugs/EndocrinologicandMetabolicDrugsAdvisoryCommittee/UCM258121.pdf

Primary Outcome

http://www.fda.gov/downloads/AdvisoryCommittees/CommitteesMeetingMaterials/Drugs/EndocrinologicandMetabolicDrugsAdvisoryCommittee/UCM258120.pdf

FDA is requiring the manufacturer of Trilipix to conduct a clinical trial to test the hypothesis that Trilipix in combination with a statin versus statin alone significantly reduces the incidence of major adverse cardiovascular events in high-risk men and women who are at their LDL cholesterol goal on statin therapy, but have residually high triglycerides and low HDL cholesterol.

FDA Decision

Additional Information for Patients

◦ Trilipix has not been shown to lower patients' risk of having a heart attack or a stroke.

◦ Patients should not stop taking their Trilipix medicine without first consulting with their healthcare professional.

◦ Patients should discuss the benefits and risks of taking Trilipix with their healthcare professional.

◦ Patients should read the Medication Guide that they get along with their Trilipix prescription.

◦ Patients should talk to their healthcare professional if they have any questions or concerns about Trilipix.

◦ Patients should report serious side effects from the use of Trilipix to the FDA MedWatch program, using the information in the "Contact Us" box at the bottom of this page.

FDA Decision

Additional Information for Healthcare Professionals 

◦ Fenofibrate at a dose equivalent to 135 mg of Trilipix was not shown to reduce coronary heart disease morbidity and mortality in patients in two large randomized controlled trials of patients with type 2 diabetes mellitus.

◦ Healthcare professionals should consider the benefits and risks of Trilipix when deciding to prescribe the drug to patients, and counsel patients about those benefits and risks.

◦ Healthcare professionals should encourage patients to read the Medication Guide they receive along with their Trilipix prescription.

◦ Healthcare professionals should report adverse events involving Trilipix to the FDA MedWatch program using the information in the "Contact Us" box at the bottom of this page.

FDA Decision

Medical Guid

http://www.fda.gov/downloads/Drugs/DrugSafety/ucm089806.pdf