FDA: No Cardiovascular Event Reduction Claim for Ezetimibe
The US Food and Drug Administration has declined to extend the indication for the cholesterol-lowering drug ezetimibe to include cardiovascular event reduction, the manufacturer has announced.
Merck received a complete response letter from the agency on Monday, signaling that the FDA would not be approving its supplemental new drug application in its current form.
Following the positive results from IMPROVE-IT, a large morbidity and mortality trial, the company was seeking a claim that ezetimibe reduced the risk of cardiovascular death, nonfatal MI, nonfatal stroke, hospitalization for unstable angina, or need for revascularization in patients with coronary heart disease. The company said in a statement that it is reviewing the FDA’s letter “and will determine next steps.”
The FDA decision follows the recommendation of the Endocrinologic and Metabolic Drugs Advisory Committee who voted 10-5 that the safety and efficacy data from IMPROVE-IT did not support the expanded indication for CV event reduction.
In that trial, adding ezetimibe to simvastatin 40 mg significantly reduced the primary composite endpoint by 6.4% when compared with patients who received simvastatin alone—a reduction driven by a statistically significant reduction in the risk of MI and ischemic stroke. The absolute difference in the primary endpoint, however, was a modest 2.0%, which left committee members struggling—in the words of one panelist—“with the clinical meaningfulness of the treatment effect.”
Ezetimibe is currently marketed as Zetia, or in combination with simvastatin as Vytorin, and is indicated for the reduction of elevated total cholesterol, LDL cholesterol, apolipoprotein B, and non-HDL cholesterol in patients with hyperlipidemia when diet alone is not enough.
Merck receives complete response letter from the U.S. FDA for Zetia® (ezetimibe) and Vytorin® (ezetimibe and simvastatin) [press release]. Published February 15, 2016. Accessed February 17, 2016. http://www.mercknewsroom.com/news-release/prescription-medicine-news/merck-receives-complete-response-letter-us-fda-zetia-ezetimi.