Last Friday, Genzyme and Isis Pharmaceuticalsdisclosed that the FDA wants them to gather more data in order to win approval for a novel cholesterol drug. Specifically, the agency indicated that lowering cholesterol is an "acceptable surrogate endpoint" for using their mipomersen in patients with a rare, inherited form of high cholesterol. But an outcomes trial will be needed to win approval for other patients with high cholesterol. Such a trial can prove valuable if the outcome is achieved, but it's also expensive and time-consuming because many more patients are needed to enroll.
Interestingly, Zetia was approved six years ago on its ability to lower cholesterol, but actual outcomes data for Vytorin still isn't available. We mention both drugs in the same breath because Zetia, of course, is one part of the Vytorin cholesterol combo sold by Merck and Schering-Plough; the other part is Zocor. And the results of a study that is designed to show that Vytorin can outperform Zocor alone in preventing deaths, heart attacks and strokes won't be released until 2012, at the earliest.
You may recall that the controversial Enhance study used a surrogate endpoint - carotid intima-media thickness (IMT) - because people with thicker IMT in the carotid artery have a higher risk of cardiovascular events. But the Enhance trial found that Vytorin failed to show any benefit over the much cheaper Zocor in reducing the plaque in the carotid artery, and even showed a statistically insignificant buildup, although it did a better job of lowering LDL in a small group of patients with inherited high cholesterol.
In a recent commentary in the Journal of the American Medical Association, Bruce Psaty and Tom Lumley of the University of Washington wrote that "the public health advantages of rapid approval for drugs that turn out to be safe and effective need to be balanced against harms that might occur when drugs approved on the basis of surrogate end points turn out later either to have significant safety problems or to lack efficacy."
Given the concerns over how widely marketed Vytorin and Zetia were over the past few years, the FDA response to Genzyme and Isis raises an interesting thought - whether the agency is no longer willing to approve new drugs for wide use based solely on the ability to improve cholesterol. What do you think?
Should the FDA require outcomes data?
- Yes (66%, 57 Votes)
- No (34%, 29 Votes)
Total Voters: 86