How much damage did ENHANCE cause for Merck and Schering Plough’s Vytorin?

After much delays and controversy due to attempts to re-consider the study ENHANCE end point, top line results have been released according to the initial design. Bottom line: Vytorin, a fixed combination of 10 mg of ezetimide, a cholesterol absorption inhibitor, and 80 mg simvastatin did not due better than 80 mg simvastatin alone in reducing Intima Media Thickness (IMT) or atherosclerotic plaque at 3 sites in the carotid arteries in patients with Familial Hypercholesterolemia. Meanwhile, LDL-C, a key marker of heart disease, was down 68% at 24 months in the Vytorin group versus 41% in the simvastatin group. What can we conclude? Atherosclerosis is multi-faceted and particularly difficult to study. Statins anti-inflammatory effect – in addition to LDL-C lowering- may be a significant contributor to their efficacy. Inflammation is a key component of atherosclerosis and heart disease. Vytorin remains a safe and superior efficacy drug to agressively reduce LDL-C.  Dr Steven Nissen, a leading cardiologist from the Cleveland Clinic and often critic of the industry, recommended to limit the use of Vytorin to patients not responding to simvastatin. We believe hat this is an over-reaction since LDL-C remains the best marker of heart disease prevention and  the consensus is that “lower is always better”.

More definitive conclusions will determine the long term future of Vytorin when the results of three larger cardiovascular end pont studies are available in 2010-11.

Merck & Co  (NYSE:MRK) and Schering Plough (NYSE:SGP) have been down 1.3% and 8% respectively on January 14 upon release of the unfavorable news. Negative publicity for Vytorin may have a short term impact on sales but long term Vytorin remains a winner and a major revenue contributor for both Merck and Schering Plough.

Schering Plough’s CEO showed his confidence by personally purchasing $ 2 million of Schering Plough stock on the open market.