Experts Weigh in on ENHANCE Published Results

Includes: MRK, SGP
by: Fredric Cohen, M.D.

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(NYSE: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.