Re: Merck, Schering-Plough Defend Efforts for Vytorin, Zetia

New Vytorin Report Draws Fire
Matthew Herper, 01.25.08, 3:25 PM ET

For the first time, Merck and Schering-Plough have released details of
how a key study of their cholesterol drug Zetia, also used in the
combo pill Vytorin, wound up being delayed for more than a year after
its findings were originally expected. But the report has inflamed
critics rather than pacified them.

"I think it's great they're disclosing this," says Harlan Krumholz, a
cardiologist at Yale University. "I think there's nothing here that's
reassuring. It raises more concerns."

At best, Krumholz and others claim the companies bungled the research;
at worst, they say Merck and Schering-Plough may have deliberately
stalled revelations that the $5 billion cholesterol franchise did no
better than a cheap generic.

Committees from both houses of Congress are investigating the delay,
and the companies gave a similar version of the same timeline to the
House Committee on Energy and Commerce Thursday.

The company defended its actions: "While the ENHANCE trial was time-
consuming and took longer than [we had] originally anticipated to
complete, our companies acted with integrity and good faith in
connection with the trial," said Thomas Koestler, who heads research
at Schering-Plough, in a prepared statement.

Since revealing that Vytorin failed to reduce atherosclerosis better
than the cheap generic Zocor, shares of both companies have fallen.
Schering shares are down 25%, Merck shares 15%. The companies split
profits from Zetia and Vytorin 50-50, through a joint venture that
markets both pills.

In the five-page timeline released Friday, the companies say Schering-
Plough biostatisticians first became concerned about the data by the
end of 2005. These statisticians became aware of instances of what the
companies called "biologically implausible" data. Those concerns led
the company to bring in outside consultants at least a half-dozen
times, to look at the ultrasound pictures of arteries being generated
by the trial, and to deal with problematic or missing images.

But at least one of the companies' outside experts said Friday that
the data quality of the study was similar to that of other trials.
Still, the companies did even more analyses of the database, and say
they did not actually begin the process of "unblinding" the data until
Dec. 31, 2007. On Jan. 14, the companies issued the press release
detailing the long-awaited results of the study.

Krumholz still worries the delays could well have been caused by
commercial--not scientific--concerns. "By the summer of 2005, their
marketing division is so successful that it already is a blockbuster
drug. There was only downside [to analyzing the results.]"

Allen J. Taylor, head of cardiology at Walter Reed Army Medical
Center, says that, based on the release, "the fundamental question
does remain at which point they knew the study did not favor one group
over the other."

Moreover, he says, spending so long trying to clean up the data was
not appropriate in any case. "It's not liking the answer and hoping
that if you do it again you'll get a better answer," says Taylor. "The
fact they never found a good solution validates the point: The data
are the data."

In an interview Friday, John Kastelein of the University of Amsterdam,
the lead outside scientist conducting the trial, says he was not
consulted about the timeline or the press release before it was
issued. "If people want to really judge the quality of this trial,
they should wait until the data were peer-reviewed," he says. At that
point, they will be presented at a medical meeting or in a medical
journal.

Meanwhile, the American College of Cardiology, which had earlier
issued a statement warning that patients and physicians should not
draw too many conclusions from the study, issued a second statement
Friday clarifying that Zetia and the Vytorin combo pill should be used
only after other medicines with more evidence of benefit have been
tried.

Douglas Weaver, chief of cardiology at Henry Ford Hospital in Detroit
and president-elect of the ACC, says that the new statement came
partly as a response to full-page advertisements from Merck and
Schering defending Zetia and Vytorin and telling patients not to
overreact to the ENHANCE study's findings.

"It's concerning to us, because we're worried that patients who really
aren't experts and read this casually could interpret that the ACC
endorse this as a first-line therapy," says Weaver. "We do not want to
be seen as doing that. I'm kind of surprised the companies did that."


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