|
Pfizer admits
1999 trials
revealed risks with Celebrex
February 1, 2005--Celebrex, the popular arthritis and pain medicine
from Pfizer, sustained another blow Monday when the company
acknowledged that a 1999 clinical trial found that elderly patients
taking the drug were far more likely to suffer heart problems than
patients taking a placebo.
Although
the company sought to play down the trial's significance on Monday,
the disclosure of the study contradicts earlier public statements by
Pfizer, the world's largest drug maker, about the safety of Celebrex.
Concerns about the risks of Celebrex have risen since last fall,
when Merck withdrew a similar drug, Vioxx, after a trial linked it
to heart attacks.
Responding
to the Vioxx withdrawal, Pfizer had said in October said that no
completed study had ever shown any increased heart risks related to
Celebrex. Then, in December, when a colon cancer prevention study by
the company indicated that Celebrex was associated with heart
attacks and strokes, Pfizer said the results were unexpected.
Now the
company has acknowledged that the 1999 study, which was designed to
examine whether Celebrex could treat Alzheimer's disease, found
almost four times as many patients taking Celebrex for a year
suffered heart problems as those taking a placebo. Pfizer's own
analysis found the difference statistically significant.
But the
study was never published and not submitted to the Food and Drug
Administration until June 2001, four months after the FDA conducted
a major safety review of Vioxx and Celebrex's safety. Two doctors
who participated in that review said they had not known about the
1999 study until Monday. And one of them, Dr. Kenneth Brandt, a
professor of medicine at Indiana University School of Medicine, said
that if the safety panel had known about the study, the group might
have recommended that both Vioxx and Celebrex be taken with greater
caution.
That panel
decided to recommend that Vioxx, but not Celebrex, carry a warning
about its cardiovascular risks. That difference is one of the main
reasons Celebrex had greater sales than Vioxx.
Study
found on web site
The 1999
study is further evidence that Celebrex is dangerous, said Sidney M.
Wolfe, a director at Public Citizen, a consumer-advocacy group that
has asked the FDA to ban the medicine.
Wolfe
publicized the 1999 study on Monday, after finding it last week on a
new Web site where Pfizer and other drug companies have begun to
post some clinical trial results. Wolfe said the results had not
been on the site a few weeks earlier.
"It's a
clear signal that I would have loved to have known about four years
ago," he said.
But Dr.
Gail Cawkwell, Pfizer's medical team leader for Celebrex, said
Monday that the study's importance should not be overstated. Many
other trials have shown that Celebrex is safe, and that the medicine
is an important treatment for arthritis patients, she said.
Celebrex
is one of the world's most widely prescribed medicines, with sales
of $3.3 billion last year. About 25 million people have taken the
drug since Pfizer introduced it in 1999, and analysts estimate that
Celebrex contributes at least $2 billion to Pfizer's pre-tax annual
profits. But its sales have slowed since the Vioxx withdrawal last
fall raised safety questions about the entire class of drugs, which
are known as COX-2 inhibitors and includes another Pfizer
medication, Bextra.
After the
1999 study was publicized Monday, Pfizer's shares fell 19 cents, to
$24.16, their lowest level since 1997. The shares have fallen 21
percent since Merck withdrew Vioxx.
Pfizer,
whose chief executive is Henry A. McKinnell Jr., has strongly
defended Celebrex's safety, calling the drug an important
alternative for arthritis patients. The company maintained that
stance Monday, saying that the 1999 trial was flawed and too small
to be meaningful.
Study
presented in 2000
Cawkwell
said Monday that the 1999 study that showed Celebrex was ineffective
in treating Alzheimer's disease had been presented at a conference
in Sweden in 2000. But she said she did not know whether the study's
safety data had been presented.
At the
time, Celebrex was manufactured by Pharmacia, not Pfizer, although
Pfizer marketed the drug. Pfizer bought Pharmacia for $60 billion in
late 2002, largely to gain complete control of Celebrex and Bextra,
another arthritis drug.
A
spokesman for Fred Hassan, Pharmacia's former chief executive,
declined to comment. Philip Needleman, one of the original
discoverers of Celebrex, did not return a phone message.
Cawkwell
said she did not know why Pharmacia did not sent the results to the
FDA in time for the broader review. After Pfizer bought Pharmacia,
it assured patients and doctors that it had no evidence that
Celebrex was dangerous.
Vioxx
reaction
On Oct. 1,
following Merck's decision to withdraw Vioxx, Pfizer said in a press
release, "The evidence distinguishing the cardiovascular safety of
Celebrex has accumulated over years in multiple completed studies,
none of which has shown any increased cardiovascular risk for
Celebrex."
In fact,
the 1999 Alzheimer's study had found that 22 out of 285 patients
taking Celebrex suffered heart attacks, strokes and other heart
problems. Only three of 140 patients taking a placebo had suffered
similar problems. Even accounting for the difference in the sizes of
the two groups, Celebrex users were almost four times as likely to
suffer heart problems.
In the
study, patients took 400 milligrams of Celebrex daily, a dose
commonly used by arthritis patients. "A statistically significant
difference favoring placebo in adverse events was observed," the
study's authors explained.
Cawkwell
said the difference might have resulted from the fact that the
Celebrex patients in this trial happened to be sicker than patients
given the placebo. That difference was unintentional and due solely
to random chance, she said. "The patients had very different
cardiovascular histories," she said. |