New data fails to quiet cholesterol drug debate

By Julie Steenhuysen

CHICAGO (Reuters) - New data about the controversial cholesterol fighter Vytorin failed to quell concerns that the drug might not be as good as thought at keeping heart disease at bay, leading an expert panel to recommend on Sunday that patients stick with statins.

Full results of the study known as Enhance, released earlier on Sunday, mirrored results in January released by the drug's makers Merck & Co and Schering-Plough Corp <SGP.N that found the combination drug failed to show it worked any better than a cheaper generic statin at reversing heart disease.

That sent shock waves among heart doctors, who had readily prescribed the drug because it does such a great job at lowering low-density lipoprotein, or LDL, the so-called bad cholesterol doctors see as the chief villain in the war against heart disease.

The results do little to ease investor concerns about the profit potential for the drug that is critical to the future of both Schering-Plough and Merck. The two drugmakers have come under fire from the medical community and lawmakers for a long delay in releasing the results of the clinical trial.

The full study was published online in the New England Journal of Medicine and presented at a meeting in Chicago of the American College of Cardiology in a panel debate.

Vytorin combines the statin Zocor, known generically as simvastatin, with another cholesterol medicine, Zetia or ezetimibe, and is marketed by a joint venture of Merck and Schering-Plough.

Although the combination drug did a far better job at lowering cholesterol than Zocor alone, neither drug helped reduce the thickness of artery walls in patients with a condition known as heterozygous familial hypercholesterolemia, which causes very high levels of LDL.

Given the lack of evidence of a benefit, the ACC panel recommended that doctors first put patients on a high dose statin, and then try other drugs before reaching for Vytorin or Zetia. "The strongest recommendation you could make on this panel is to turn back to statins," said panelist Dr. Harlan Krumholz of Yale University, summing up the panel's recommendation.

"We were very disappointed in the ACC panel. We had expected a balanced discussion and we really didn't think the panel today served patients well," Dr. Robert Spiegel, chief medical officer of Schering-Plough told Reuters.

Dr. John Kastelein, the Dutch researcher who led the Enhance study, said in an interview he fully expected the results to be positive, and was shocked when he learned the final outcome of the study in January.

"I fell off my chair. Honestly. I would have never expected it," Kastelein said. He said there were many possibilities about why the drug did not show a benefit, but said the Enhance study was only designed to answer the question of whether one drug that lowers cholesterol worked better than another.

"I think everybody in his right mind thought it is LDL that counts. A study like this makes you shiver a bit," Kastelein said.

Dr. Greg Brown of the University of Washington in Seattle said the study challenged long-held assumptions about the value of lowering LDL cholesterol.

"We've always assumed no matter how you get the LDL down, it's good," Brown said in an interview.

While the Enhance study raises a number of questions, he said it does not answer them. "For now, the study's findings are a red flag, but not a 'black box'," Brown and colleagues wrote an editorial in the New England Journal of Medicine, referring to the strongest warning label possible that U.S. health regulators can put on a prescription drug.