Experts Weigh in on ENHANCE Published Results

This is a follow up to the piece I wrote in January describing the preliminary (but widely publicized) results from the ENHANCE study of simvastatin and ezetimibe (Zetia) (combination tablet sold as Vytorin by Schering-Plough(SGP) and Merck(MRK)) in patients with familial hypercholesterolemia.

The study looked at the effects of the combination versus simvastatin alone on carotid intima-media thickness. My previous opinions of the study’s meaning aren’t changed with publication of the final results in the NEJM to coincide with the ACC meeting. In case you were asleep for the past couple of months, ENHANCE was negative for signs of IMT improvement with the combo.

Expert opinion of the findings has been decidedly negative and prescriptions for Ezetimibe (a $5 billion a year drug, counting both Zetia and Vytorin) have tumbled. Schering-Plough reported that scripts were 3.2 million in January and 2.8 million in February for both drugs combined (a 12.5% drop), while others have reported that Vytorin scripts have fallen 18%.

Several sell-side analysts believe the latest pronouncements from experts at the ACC will further erode sales of Zetia and Vytorin and have cut their sales forecasts and share-price targets for Merck and Schering-Plough. Given the overreaction to the results thus far, it’s hard to find fault with their reasoning.

I await results from ongoing studies (particularly IMPROVE-IT) with hard CV outcomes as the primary endpoint in a less highly selected population before changing my own use of Zetia. If Ezetimibe doesn’t work to reduce hard CV outcomes despite robust LDL-C reductions, the findings will be strong evidence supporting pleiotropic benefits of statins and arguing against routine use of Ezetimibe. If Ezetimibe does work, the utility of CIMT progression in hypercholesterolemia will be dubious.

Comments

[User 171364:]

Dr. Cohen- you used the word "overreaction" in your story. I agree that it is unbelievable what has occurred as a result of .01 millimeters in patients who apparently didn't have much carotid thickness to begin with. So the question is: if you think it is an overreaction and I think it is an overreaction.......why are the cardiologists at ACC overreacting?

2008 Apr 01 07:14 PM

[WaveNet Pharma:]

A PERSONAL EXPERIENCE

After taking Mevacor and Tricor for 20+ years without success in lowering my Cholesterol I was switched to Vytorin which produced the best results ever, including amazingly low LDL.

When my new health insurance denied Vytorin and recommended Zocor instead I pointed out to them the need to combine Zetia with Zocor to produce the same effect.They agreed.

Now the Economics : 90 days of supply between the two alternatives compares as follows: VYTORIN ( $245) vs ZOCOR + ZETIA ( $393+$240). When the insurance discovered that nothing was as cost-effective as Vytorin for my treatment needs, they have re-instated coverage in a hurry and presented an apology.

In conclusion, for those patients who are in my situation and need the two components, nothing beats Vytorin in convenience and economics.

The death of Vytorin and the hit on SGP has been grossly exaggerated.Does anyone believe that those who are on it already will switch out to others ?

If we assume a no growth scenario and a preservation of the existing patient population, SGP could jump at least 50% from its currently depressed valuation. If they hire smarter people to run the company and their marketing effort, the upside is even larger. I see $24 by YE as a reasonable target.

2008 Apr 03 01:11 AM