Schering, Merck's Vytorin Should Be Last Resort, Doctors Say

By Shannon Pettypiece and Michelle Fay Cortez

March 31 (Bloomberg) -- Millions of people taking Schering- Plough
Corp. and Merck & Co.'s cholesterol pill Vytorin should instead be
getting older drugs proven to reduce the risk of death, according to
top U.S. heart doctors.

The advice, from a panel that reviewed the data for the American
College of Cardiology, follows release of a study at the physician
group's annual meeting yesterday in Chicago. That finding showed that
Vytorin, prescribed 20 million times last year, didn't slow the
clogging of arteries better than Merck's Zocor, sold generically for a
fifth of the cost.

The panel's recommendation may further reduce Vytorin prescriptions,
which have fallen 18 percent since a preliminary report on the
research was published in January. Studies show cholesterol drugs
called statins, including Pfizer Inc.'s Lipitor, prevent heart attacks
and strokes, while trials to make similar claims for Vytorin won't be
completed until 2012.

``This study provides no new evidence to support the use of this drug,
and it moves us to more uncertainty about the benefits,'' said Harlan
Krumholz, a cardiologist at Yale University, who spoke for the panel.
``You've just seen a clinical trial that should change practice.''

Vytorin combines Zocor with the companies' other cholesterol drug,
Zetia. The two medicines had more than $5 billion in sales last year.
The study, called Enhance, was designed to give Schering-Plough, of
Kenilworth, New Jersey, and Whitehouse Station, New Jersey-based Merck
a greater share of the $35 billion worldwide cholesterol market.

Treatment Option

``We believe Vytorin and Zetia should continue to be a therapeutic
option,'' said Rick Veltri, Schering-Plough's vice president of global
clinical development for cardiovascular and metabolic disease, in an
interview.

``It is going to be tough to promote the drug without any evidence
that it provides a benefit,'' said Michael Krensavage, an analyst with
Raymond James in New York, in a telephone interview. ``People were
hoping to see a glimmer of evidence that Zetia can save lives and it
is very hard to find that glimmer of hope among these data.'

Merck and Schering-Plough have said doctors should focus on Vytorin's
ability to lower cholesterol in the blood more than simvastatin, the
generic form of Zocor, can accomplish alone. They also said the
study's results shouldn't be applied to the mainstream population
because the research only looked at patients with a rare genetic
condition that causes them to produce excess cholesterol.

Physician Panel

Along with Yale's Krumholz, the panel that reviewed the study included
Joseph Messer, a cardiologist at Rush University in Chicago, Patrick
O'Gara, the vice chairman of clinical affairs at Brigham and Women's
Hospital in Boston, and Rick Nishimura, a cardiologist at the Mayo
Clinic. The panelists chosen had no personal financial conflicts of
interest, the ACC said.

The four cardiologists discussed the data before the meeting, and
reached the conclusion that doctors should rein in their use of
Vytorin and Zetia and only prescribe the drugs after other treatments
fail. They reviewed their recommendations after the study's findings
were released at the ACC meeting.

``This means that Zetia and Vytorin are not first-line drugs and I'm
afraid some people have been using them that way,'' said Douglas
Weaver, president-elect of the American College of Cardiology and
director of the Cardiovascular Institute at the Henry Ford Health
System in Detroit. ``It sends out the message that there has been
overuse.''

About $49 billion in the companies' combined market value has been
wiped out since the preliminary results were reported. Merck fell 27
cents to $44.51 in New York Stock Exchange composite trading on March
28. Schering-Plough gained 17 cents to $19.47.

Cause Unknown

The ultimate cause for the lack of benefit remains unknown,
researchers wrote in the New England Journal of Medicine. The results
were particularly surprising since Vytorin reduced levels of bad
cholesterol significantly more than Zocor, known generically as
simvastatin, alone.

It is unlikely the drug would have a benefit on the heart, even in
lowering cholesterol, if it didn't reduce plaque buildup, wrote Allen
Taylor, head of cardiology at Walter Reed Army Medical Center and B.
Greg Brown, a cardiologist at the University of Washington School of
Medicine in Seattle, in an editorial accompanying the study.

The chance that the pill provides no benefit, ``which is the elephant
in the parlor, deserves serious consideration in any discussion of the
results of the study,'' Taylor and Brown wrote. ``For now, the study's
findings are a red flag but not a black box.''

700 Patients

The Enhance study looked at about 30,000 pictures of the arteries of
more than 700 patients, half on Zocor and half on Vytorin, to
determine whether there was less plaque buildup in the Vytorin group
after two years.

Results from a separate study, which will measure whether patients are
less likely to have a heart attack or stroke on Vytorin, won't be
available until 2012.

That study was delayed by a year because the researchers said last
week they wanted to increase the number of patients involved by about
80 percent to 18,000 to ensure they would be able to detect any
difference in outcomes.

The drug was heavily marketed to doctors and patients, including a
$140 million-a-year ad campaign with people dressed to resemble food
items to show how Vytorin treats cholesterol from food along with that
produced by the body because of genetics. The companies have since
halted the advertisements.

``It could also be that Zetia is just an expensive placebo and its
principal harm is it drains precious resource from our health-care
system and may lead people to use less of the drugs that we know are
effective and beneficial,'' said Krumholz. ``If you were put on this
drug before you had an opportunity to be fully treated on statins you
should see your doctor.''

To contact the reporter on this story: Shannon Pettypiece in New York
at spettypiece@bloomberg.netMichelle Fay Cortez in Minneapolis at
mcortez@bloomberg.net

Last Updated: March 31, 2008 00:01 EDT

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