The Wall Street Journal-20080115-Study Deals Setback to Vytorin Cholesterol Drug
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Study Deals Setback to Vytorin Cholesterol Drug
Merck & Co. and Schering-Plough Corp. said a long-awaited trial showed their cholesterol drug Vytorin failed to slow progression of heart disease better than a cheaper drug, threatening the companies' $5 billion-a-year cholesterol-fighting franchise.
Schering-Plough's shares fell 8% to $25.52 and Merck declined 1.3% to $59.78 at 4 p.m. in New York Stock Exchange composite trading.
Vytorin and its sister drug, Zetia, are widely used to reduce bad cholesterol beyond what popular anticholesterol drugs known as statins can do alone. Vytorin, which is heavily marketed in direct-to-consumer advertising, consists of Zetia and a statin, Zocor, combined into a single pill.
However, the companies have yet to demonstrate that Vytorin and Zetia can prevent deaths or heart attacks better than a statin alone. The question has big economic significance because several statins, including Zocor, are available in generic form for around $1 a pill or less, while Vytorin costs around $3 a pill.
Schering-Plough and some analysts played down the significance of the study.
"Of course we would have preferred a more positive result, but in some ways the results are not totally surprising," said Robert Spiegel, Schering-Plough's chief medical officer. He said the companies "had set a high hurdle" by testing it in a high-risk patient population with a genetic variant that raises the patients' cholesterol far beyond what is normal in the general population.
But Steven E. Nissen, chairman of cardiovascular medicine at the Cleveland Clinic, said the results suggest "physicians should now stop using [Zetia] or Vytorin as a primary therapy for patients with high cholesterol."
The study, called Enhance, was completed in April 2006. The long- delayed publication of its results has drawn scrutiny in the media and Congress in recent weeks. In November 2007, the companies announced plans to change the trial's primary measure of effectiveness to expedite their analysis, but they reversed course last month after critics said the switch was a breach of scientific protocol.
Zetia works by blocking absorption of bad cholesterol, known as low- density lipoprotein or LDL, from food in the intestinal tract. Statins reduce bad cholesterol by interfering with its production in the liver.
Studies have shown that adding Zetia to a statin further reduces bad cholesterol by 15% to 20%. Many doctors prescribe Zetia or Vytorin as an alternative to raising the dose of a statin.
The two-year Enhance study of 720 patients aimed to provide a clue about whether that strategy can prevent the progression of cardiovascular disease. Researchers measured the accumulation of fatty deposits called plaque in patients' carotid, or neck arteries -- an established indicator of heart-disease risk. They compared results for patients taking Vytorin versus those taking only the statin Zocor.
The result: essentially no difference between the two groups. Both treatments stopped the accumulation of plaque but didn't significantly reverse it.
Merck and Schering-Plough have been playing down the study in recent weeks. At a conference hosted by Morgan Stanley earlier this month, Schering-Plough Chief Executive Fred Hassan said Enhance was "not a large trial" and was "in a very, very special" population. He added, "I don't know why this would have any impact on mainstream use" of Vytorin.
But some cardiologists counter that assertion. "If a group of patients with LDL levels this high don't benefit" from Vytorin, Dr. Nissen said, "who's going to benefit?"
Col. Allen J. Taylor, chief of cardiology service at Walter Reed Army Medical Center, pointed to research suggesting that raising the dose of a statin can add to the impact on plaque in the arteries -- the result Zetia failed to achieve in the Enhance study. "If we don't pay attention to that, we're making a mistake," said Col. Taylor.
Other cardiologists said they would stick with Zetia, at least for certain patients -- for instance, those who are at risk of side effects from a high statin dose.
"We treat based [on] goals rather than [on] specific drugs," said Michael Davidson, director of preventive cardiology at the University of Chicago's Pritzker School of Medicine. "That's the important message that is not changed by this trial." Dr. Davidson worked on some trials that supported FDA approval of Vytorin and Zetia.
Schering-Plough's Dr. Spiegel says the company believes Zetia and Vytorin provide substantial benefits to patients. "There shouldn't be a burden of proof on us to re-establish 20 years of medicine, that lowering LDL is good for you and is good for patients with high risk factors for cardiovascular disease," Dr. Spiegel said.
The Food and Drug Administration also is likely to face questions about how the drug was approved and promoted. An FDA spokeswoman said the agency is evaluating data from the Enhance study.
Reps. John Dingell and Bart Stupak, both Michigan Democrats, said they planned to keep probing Enhance. "Merck and Schering-Plough's delay in releasing study results, as well as their attempt to manipulate the data is, quite frankly, suspicious," Mr. Dingell said. "We will continue our investigation until these questions are answered."
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Anna Wilde Mathews contributed to this article.
