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DBL%20Hendrix%20small.png College chemistry, 1983

Derek Lowe The 2002 Model

Dbl%20new%20portrait%20B%26W.png After 10 years of blogging. . .

Derek Lowe, an Arkansan by birth, got his BA from Hendrix College and his PhD in organic chemistry from Duke before spending time in Germany on a Humboldt Fellowship on his post-doc. He's worked for several major pharmaceutical companies since 1989 on drug discovery projects against schizophrenia, Alzheimer's, diabetes, osteoporosis and other diseases. To contact Derek email him directly: Twitter: Dereklowe

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March 24, 2014

Ezetimibe In the Marketplace

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Posted by Derek

Several years ago, the Schering-Plough cholesterol absorption inhibitor (Zetia, ezetimibe) and its combination pill with simvastatin (Vytorin) were the subject of a lot of puzzled controversy. A clinical trial (ENHANCE) looking at arterial wall thickness in patients with familial hypercholesteremia had unexpectedly shown little or no benefit, although statins themselves had worked in this population. This led to plenty of (still unresolved) speculation about the drug's mechanism of action, whether it really was going to be of benefit to the wider patient population, what this meant for the surrogate endpoint of LDL lowering (which the drug does accomplish), and so on.

Sales of both Zetia and Vytorin took a hit, naturally. But a new editorial in JAMA wonders why they're selling at all, and particularly, why they're doing so well in Canada. A new paper in the American Heart Journal shows that ezetimibe sales in the US went down 47% over the next year after the ENHANCE results came out. But in Canada, it just kept rolling along. (Even after the decline, though, it's still used more in the US).

What's causing this? Quite likely, an over-focus on cholesterol levels themselves:

Krumholz, one of the coauthors on the study with Jackevicius, remains perplexed as to the continuing popularity of ezetimibe. “The drug continues to defy gravity, and that’s probably a result of really strong marketing and the singular focus on cholesterol numbers,” he said.

Krumholz said heart health campaigns urging patients to “know your numbers” and treatment goals based on cholesterol measurements, such as getting asymptomatic individuals’ LDL-C levels below 130 mg/dL, have worked in ezetimibe’s favor at the expense of evidence-based medicine. “Is this the drug that lowers your LDL-C and helps you? We don’t know that,” he said. “The comfort of hitting a target offers little benefit if you don’t know that it is really protecting you.”

The funny thing is, all that emphasis on LDL assay numbers was supposed to be "evidence-based medicine". But that's the funny thing about science - the evidence keeps leading you in new directions.

Comments (4) + TrackBacks (0) | Category: Cardiovascular Disease


1. Barry on March 24, 2014 10:07 AM writes...

it's not dissimilar to the continued billions spent/made on bisphosphonates. An over-focus on density measured on x-ray (the surrogate marker) rather than on bone-strength (the problem they were supposed to treat) has kept them in use and has stolen the incentive to find/develop better therapeutics.

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2. Anon on March 24, 2014 12:13 PM writes...

I believe many people, mostly physicians and patients, don't realize that evidence based medicine is often correlative based medicine. While it is STRONGLY correlative and a MUCH better option than the alternative, everyone needs to recognize that marketing folk dig their heals into a specific "mechanism" and physicians learn most of what they know from either their initial residency training, the occasional talk they hear at a continuing education conference, or information from a drug rep(which only happens if there is a new drug, obviously).
I've listened through enough physician interviews (to gauge marketability, price points, recommendations, etc.) to recognize that many are very slow in changing their ways (maybe they would call this being conservative) and often do not proactively seek out information on new treatments regimens or therapies. They seem to take the approach of being very content in their knowledge and cautiously listen to drug reps, which again is only helpful if there is a new drug out.

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3. Anon on March 26, 2014 12:29 PM writes...

So when does the outcome study result become public?

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4. Guppy on March 27, 2014 2:48 PM writes...

@Barry: Just so our other readers don't get the wrong idea -- although bisphosphonates raise one specific (and rare) class of femoral fracture, the overall fracture rate goes down.

This is because hip fractures and vertebral compression fractures (which bisphosphonates appear to reduce) are much more common to start with, so the proportional changes there make a bigger impact.

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