FDA Says Cancer Risk With Ezetimibe Is Unlikely

December 22, 2009

December 22, 2009 (Washington, DC) — The Food and Drug Administration (FDA) has completed its review of the possible link between ezetimibe (Zetia, Merck/Schering-Plough Pharmaceuticals), the combination of ezetimibe and simvastatin (Vytorin, Merck/Schering-Plough Pharmaceuticals), and an increased risk of cancer and cancer-related deaths. It concludes that the ezetimibe is likely safe.

"Based on the currently available information, the FDA believes it is unlikely that Vytorin or Zetia increase the risk of cancer or cancer-related death, but at this time an association cannot be definitively ruled out," according to a statement on the FDA's website.

The review was based on findings from the Simvastatin and Ezetimibe in Aortic Stenosis (SEAS) trial, a study that missed its primary end point when the combination failed to reduce the composite end point of aortic-valve and cardiovascular events but showed that significantly more subjects treated with Vytorin developed and died from all types of cancer when compared with those taking placebo during the five-year study.

In addition to SEAS, the completed FDA review included an interim analysis of two ongoing studies with ezetimibe: the Study of Heart and Renal Protection (SHARP) and the Improved Reduction in High-Risk Subjects Presenting with Acute Coronary Syndrome (IMPROVE-IT) trial. The review is a follow-up to the August 2008 "early communication" about the safety of ezetimibe and simvastatin that was spurred by data from the SEAS trial. The interim review was reported by heartwire , as was an independent cancer analysis performed by researchers at Oxford University.

The agency said it weighed several factors when evaluating the association between the use of ezetimibe and cancer risks. It notes that preclinical studies with ezetimibe showed no increased incidence of cancer, that the risk of cancer did not increase consistently with longer drug exposure in SEAS, as would be expected if a drug caused cancer, that it did not promote the growth of existing tumors, and that it is biologically less plausible that an agent increases the risk of a wide variety of cancer types, as also observed in SEAS.

It adds that the three trials combined--SEAS, IMPROVE-IT, and SHARP--showed no consistent pattern of increased cancer risk among those treated with the ezetimibe/simvastatin combination. The SHARP trial is expected to be completed in 2010 and IMPROVE-IT in 2012.

"The FDA is not advising healthcare professionals or consumers to stop using these medications but to continue to evaluate the clinical benefits and potential risks of Vytorin or Zetia compared with other FDA-approved cholesterol lowering medications," according to the agency. "Consumers should talk to their healthcare professional if they have any questions about Vytorin, Zetia, Zocor [simvastatin] or the SEAS trial."