July 26, 2005
Vioxx Posed Heart Risk After Just A Few Weeks, Data Suggest
By BARBARA MARTINEZ and ILAN BRAT
Staff Reporters of THE WALL STREET JOURNAL

As pharmaceutical giant Merck & Co. battles its first court case
related to Vioxx in Texas, the company is gearing up for what could be
an even tougher fight in a New Jersey state court in September.

Plaintiff's attorneys are expected to use a document, released last
week in the Texas court case, to undermine one of Merck's main defenses
in its planned litigation strategy: that users of the painkiller Vioxx
weren't at increased risk for heart attack or stroke until after using
it daily for 18 months.

An internal company document that Merck provided to plaintiffs
attorneys suggests that some Vioxx users began experiencing more heart
problems than placebo takers as early as a few weeks after beginning to
take the painkiller.

The document -- which contains preliminary, unpublished results of a
clinical trial called Victor -- suggests that the elevated risk grew
over time. The risk neared statistical significance at about the
one-year point. Reaching statistical significance means the phenomenon
isn't due to chance. Armed with the new data, plaintiffs attorneys are
expected to argue that even patients who took Vioxx for a short period
may have been at risk for heart trouble.

Researchers at Oxford University in the United Kingdom conducted the
Victor study and while scientists there gave the company preliminary
data, they haven't yet provided the full results. "We have asked for it
more than once," said a spokesman for Merck's attorney. A company
spokeswoman added that "Merck believes that Oxford is working
diligently to get us the data as it becomes available."

Oxford said in a statement that the data are being "cleaned" and will
be submitted to Merck this Friday, "as previously agreed with Merck."
It says the final results likely won't be published until 2008.

A Merck spokeswoman cautioned that "one cannot draw scientifically
meaningful conclusions based on small amounts of data from a
prematurely terminated study."

Merck ended the Victor study last September -- and voluntarily took
Vioxx off the market -- after preliminary results of another study,
called Approve, showed a heightened risk of heart attack and stroke in
Vioxx users after 18 months, though the numbers were small. The
difference didn't become statistically significant until after 30
months, a point that Merck is now emphasizing, particularly in the case
under way, in Texas state court.

That Vioxx may have posed an increased risk even earlier could have
major implications for the legal cases being filed against Merck. Out
of 20 million Americans estimated to have taken Vioxx, only a small
percentage of them are likely to be able to claim that they took the
painkiller every day for more than a year and a half. The Victor
results could provide ammunition for those litigants who took Vioxx for
shorter periods of time.

Merck's liability has been estimated at between $4 billion and more
than $20 billion.

Merck points out that the Victor results are still tentative, and that
preliminary results for another clinical trial it halted last year,
called Vip, didn't show an increased risk for Vioxx. In fact, 15
patients on placebo had adverse cardiovascular events, compared with 14
who actually took the drug.

According to the newly released document, a Merck researcher last
February created a graph that showed the results of the Victor trial
based on the information that the company had at the time. Though the
numbers were small, the graph showed an almost immediate and wide
difference in "thrombotic cardiovascular events," such as heart
attacks, between Vioxx and placebo users. After six months, the Vioxx
users had experienced eight "thrombotic" events, compared with three on
placebo. After a year, 10 Vioxx users had thrombotic events, versus
three in the placebo group.

By the time the trial was halted, after 24 months, there were 12 events
reported among Vioxx users compared with four events in the placebo
group. The Victor trial enrolled more than 2,300 patients -- a similar
number to those enrolled in the Approve study, which led to the drug's
withdrawal. "We're still double-checking the programs," said the Merck
researcher in an email about the Victor data, "but I don't expect the
overall picture to change."

A spokesman for Merck's lead outside attorney said that the number of
thrombotic events on the graph are accurate, but emphasized that not
all the data have been received. Based on the information available to
Merck, he said, the difference at six months wasn't statistically
significant and thus could have been due to chance, while the
difference at one year was "almost" statistically significant. The
company said that interpretation of the magnitude and importance of the
results will be made more difficult by the early halt of the study.

Ted Mayer, Merck's lead outside attorney, in a statement acknowledged
that in the Victor study, the rate of events on Vioxx was higher than
placebo, but he noted that in the Vip trial, the rates were lower,
though not by much. In addition, he said the Victor trial results have
to be weighed against four other studies: Approve, Vip and two studies
of Alzheimer's patients that did not show an increased risk of heart
attacks or strokes.

The fact that there was an almost immediate difference in heart attacks
and strokes in the Victor clinical trial poses a challenge in New
Jersey state court, where Merck faces its second lawsuit in September.
In that case, Mike Humeston, an avid hiker, was 56 when he took Vioxx
for knee pain in 2001. Two months later, he suffered a heart attack,
according to his lawyer Christopher Seeger, of Seeger Weiss in New
York. Mr. Humeston survived, but his heart is permanently damaged and
he can no longer do the rugged physical activities he used to enjoy,
Mr. Seeger said.

Mr. Seeger says his client was very healthy before taking Vioxx, having
low cholesterol and low blood pressure and no history of heart disease.
Mr. Seeger says that the fact that only one of Mr. Humeston's heart
vessels appeared to be damaged after his heart attack is a sign that he
didn't have longstanding heart disease. Mr. Humeston declined to
comment. In New Jersey, Mr. Seeger only has to prove that Vioxx
contributed to his client's heart attack to win.

The Victor trial "is absolutely going to play a role" in the Humeston
trial, said Mr. Seeger. "The most important part of Victor is the lines
beginning to separate almost immediately."

In a statement, Mr. Mayer said, "We do not believe Vioxx could or did
cause his heart attack."

Meanwhile, in the Texas case yesterday, plaintiff attorney Mark Lanier
surprised Merck by announcing that he was planning to put the coroner
on the stand, even though Merck attorneys have never deposed her. The
coroner wrote on the death certificate that 59-year-old triathlete
Robert Ernst died of an arrhythmia, an irregular heart beat. Since
Merck has said there is no scientific evidence to link Vioxx with
arrhythmias, Mr. Lanier has been trying to show that Mr. Ernst had a
heart attack first, which caused an arrhythmia that led to his death.
Mr. Lanier said that the coroner's testimony will help his case
substantially. "We are not worried about the testimony," a Merck
attorney said in a statement.