FDA Issues Early Communication about an Ongoing Review of Vytorin

The U.S. Food and Drug Administration today issued an Early Communication regarding the agency’s ongoing review of Vytorin based on preliminary results from a recently completed study.

The FDA is informing the public that the agency will conduct a review of Merck and Schering Plough’s recent trial once the FDA receives the final study results.

Merck/Schering Plough Pharmaceuticals issued a press release reporting preliminary results of the study and stated that the study demonstrated no significant differences between the combination product and Zocor on the build up of cholesterol plaque in the carotid (neck) arteries. The study was not designed to detect any difference in risk of having a heart attack or stroke between the two treatments. An ongoing trial called — Improved Reduction of Outcomes: Vytorin Efficacy International Trial (IMPROVE IT) — is underway which is designed to evaluate the effect of Vytorin versus Zocor on heart disease and stroke.

This Early Communication is in keeping with the FDA’s commitment to inform the public about its ongoing review of drugs. Until the FDA reviews the data, the agency advises patients to talk with their health care providers if they have questions about the ENHANCE study.

On January 14, 2008, Merck/Schering Plough Pharmaceuticals issued a Press Release reporting preliminary results from the Effect of Combination Ezetimibe and High-Dose Simvastatin vs. Simvastatin Alone on the Atherosclerotic Process in Patients with Heterozygous Familial Hypercholesterolemia (ENHANCE) trial. This trial was designed to evaluate the amount of atherosclerotic plaque in blood vessels located in the neck based on images obtained through ultrasound in patients treated with Vytorin (ezetimibe plus simvastatin) or simvastatin alone.  Merck/Schering Plough Pharmaceuticals, the company that conducted the trial, stated that there was no significant difference between Vytorin and simvastatin in the amount of atherosclerotic plaque in the inner walls of the carotid (neck) arteries despite greater lowering of LDL-cholesterol (bad cholesterol) with Vytorin compared to simvastatin.  FDA has not received a final study report and at this time it is not clear why the lower levels of LDL cholesterol in the patients who took Vytorin did not lead to lesser amounts of plaque compared to patients treated with simvastatin alone.

An elevated LDL-cholesterol level is an established risk factor for heart disease and many studies have supported the conclusion that lowering cholesterol levels reduces the risk for heart attack and stroke. Ezetimibe inhibits the absorption of cholesterol in the intestine and is approved to lower LDL-cholesterol levels. Simvastatin (Zocor) is a lipid-lowering agent (“statin”) approved to reduce LDL and increase high-density lipoprotein (HDL) (good) cholesterol levels and reduce the risk of cardiovascular events such as heart attack and stroke. Vytorin is approved for reducing LDL and increasing HDL cholesterol levels. 

This early communication is in keeping with FDA’s commitment to inform the public about ongoing postmarketing drug issues.  Once Merck/Schering Plough Pharmaceuticals completes the analysis of the unblinded data from ENHANCE, it will submit a final study report to FDA. Once FDA receives the final study report, FDA estimates it will take approximately 6 months to fully evaluate the data. After reviewing the data from the ENHANCE study, and considering all other available information about the link between LDL lowering and reduction of cardiovascular events, FDA will determine whether any further regulatory action is warranted with regard to Zetia and Vytorin and also whether any changes to FDA’s current approach to drugs that lower LDL cholesterol are warranted.

Patients should talk to their doctors if they have any questions about the information from the ENHANCE trial.

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