FDA Issues Vytorin Early CommunicationJan 25, 2008 | Parker Waichman LLP
The Food & Drug Administration (FDA) weighed in on the Vytorin controversy today by issuing an Early Communication about its ongoing reviews of Vytorin, Zetia and Zocor. The FDA communication was prompted by preliminary results of the ENHANCE study that showed Vytorin was no better at preventing plaque buildup of the arteries in the neck than a statin alone.
Vytorin, which was developed and marketed jointly by Merck and Schering-Plough, was approved for use by the FDA in 2004. Vytorin is a combination of cholesterol-lowering Zetia and the statin Zocor. Statins like Zocor reduce the amount of cholesterol produced by the liver, while Zetia lessens the amount of cholesterol in food that is absorbed in the intestines. High cholesterol levels put a person at risk of developing clogged arteries – a major risk factor for heart attacks and strokes. Doctors and Vytorin users were led to believe that the drug would effectively reduce both sources of cholesterol, thereby lessening the amount of plaque build up in the arteries, as well as the risk of having heart attacks and strokes.
The ENHANCE study, which began in June 2002, focused on a group of 720 patients with a rare condition predisposing them to high cholesterol. The patients were given either Vytorin or a high dose of simvastatin, the generic form of Zocor. The ENHANCE study found that Vytorin worked no better to reduce clogged arteries than a high dose of a less-expensive, generically available statin alone. In fact, some of the Vytorin patients in ENHANCE actually developed more arterial plaque than those taking Zocor alone, putting them at an even greater risk of heart attacks and strokes.
The ENHANCE study was supposed to have been released by Merck & Schering-Plough in November 2006, but that was delayed by the companies until March 2007. Then Merck and Schering-Plough announced the release of ENHANCE would be delayed again until March 2008. The drug makers also announced that they would be changing the ENHANCE study’s endpoint – the main medical result the study was meant to measure. It is generally accepted that for a clinical trial to be effective, a study’s endpoint must be set at its beginning and remain unchanged. In December 2007, in response to the ENHANCE delays and the attempt by Merck and Schering-Plough to change the endpoint, Congress initiated an investigation of the ENHANCE study.
Merck and Schering-Plough backed off changing the ENHANCE endpoint and released the preliminary results of the study on January 14 in the form of a press release. The FDA said that once Merck and Schering-Plough complete the analysis of the unblinded data from ENHANCE, the companies will submit a final study report to FDA. From that point, it should take the FDA 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 cholesterol lowering and reduction of clogged arteries and cardiovascular events, the FDA will determine whether any further regulatory action is warranted with regard to Zetia and Vytorin. The FDA also said that once it finished its own review, it would consider whether any changes to its current approach to cholesterol-lowering drugs was warranted.
In spite of the fact that ENHANCE found that Vytorin was no more effective than a high dose of generically-available Zocor, the FDA said it was not advising healthcare professionals to stop prescribing the drug.