An FDA advisory committee rejected Merck’s claims that the combination of ezetimibe and simvastatin (Vytorin) reduces the risk of cardiovascular events such as MI and stroke compared with simvastatin alone in patients with coronary heart disease.
The panel voted 10 to 5 against Merck in a committee meeting on Dec. 14. Merck also markets simvastatin.
The members considered data from IMPROVE-IT, a multinational, randomized, cardiovascular outcomes trial that evaluated 18,144 adults at 1,147 centers. The primary endpoint was a composite of cardiovascular death, nonfatal MI, documented unstable angina requiring admission to the hospital, coronary revascularizations with PCI or CABG at least 30 days after randomization and nonfatal stroke.
The researchers found that 28.4 percent of patients in the ezetimibe and simvastatin group and 30.2 percent of patients in the simvastatin group had at least one primary composite endpoint event, which corresponded to a 6.4 percent relative risk reduction.
Merck is seeking an additional proposed indication that the combination of ezetimibe and simvastatin in patients with coronary heart disease reduces the risk of cardiovascular events, which it defines as cardiovascular death, nonfatal MI, nonfatal stroke, hospitalization for unstable angina or need for revascularization.
Ezetimibe and simvastatin, which the FDA approved in 2004, is an oral medication now approved as an adjunctive therapy to diet to reduce elevated total cholesterol, low density lipoprotein cholesterol, apolipoprotein B, triglycerides, and non–high density lipoprotein (HDL) cholesterol and to increase HDL cholesterol in patients with primary hyperlipidemia or mixed hyperlipidemia.
The FDA does not have to follow the recommendation of the advisory committee, although it often does so.
“Today’s discussion is one step in the regulatory process,” Daniel Bloomfield, MD, vice president of cardiovascular diseases at Merck Research Laboratories, said in a news release. “We believe that IMPROVE-IT showed that ezetimibe in combination with a statin offers a significant benefit to high-risk patients with coronary heart disease (CHD) and are committed to continuing to work with the FDA so that they can complete the review of our request for new indications for VYTORIN and ZETIA® (ezetimibe). We believe that the results of the IMPROVE-IT trial address an important medical need in patients on statin therapy who are high-risk for cardiovascular events.”