Merck announced that the Food and Drug Administration (FDA) has issued a Complete Response Letter regarding its supplemental New Drug Applications (sNDAs) for Zetia (ezetimibe) and Vytorin (ezetimibe/simvastatin), for the reduction of the risk of cardiovascular events (cardiovascular death, non-fatal myocardial infarction, non-fatal stroke, hospitalization for unstable angina, need for revascularization) in patients with coronary heart disease.
Zetia and Vytorin are currently indicated for use in addition to a healthy diet to lower elevated LDL cholesterol in patients with hyperlipidemia.
The applications were based on data from the IMPROVE-IT (IMProved Reduction of Outcomes: Vytorin Efficacy International Trial) that evaluated the effect of ezetimibe combined with simvastatin, as compared with that of simvastatin alone, in stable patients who had had an acute coronary syndrome and whose LDL cholesterol values were within guideline recommendations (n=18,144). Simvastatin/ezetimibe 40mg/10mg combination was compared with simvastatin 40mg and placebo. The primary endpoint was a composite of cardiovascular death, nonfatal myocardial infarction, unstable angina requiring rehospitalization, coronary revascularization (≥30 days after randomization), or nonfatal stroke with a median follow-up of 6 years.
Overall, study data showed ezetimibe, when added to statin therapy, led to an incremental lowering of LDL cholesterol and improved cardiovascular outcomes. Lowering LDL cholesterol levels below previous targets offered additional benefit.
Merck is reviewing the letter from the FDA and will determine its next steps.