http://www.latimes.com/news/nation/reports/fda/lat_posicor001220.htm
Wednesday, December 20, 2000 |
POSICOR:
143 Sudden Deaths Did Not Stop Approval
With study results kept secret, nation got another blood-pressure drug.
By DAVID WILLMAN, Times Staff Writer
Senior FDA officials with the power to approve new drugs were
warned in advance about the dangers of Posicor, a pill for high blood
pressure and symptomatic chest pain.
MUTED WARNING
Taking Posicor with certain other drugs posed a danger for heart
rhythm disturbances. The clinical studies of Posicor "cast a
shadow of potential risk for serious arrhythmias," FDA medical team
leader Dr. Shaw T. Chen wrote on Dec. 18, 1996. The data in hand also
showed Posicor would interact with certain other drugs, posing
potentially severe risk.
A 70-year-old man suffered "sudden death" in one study of
Posicor's effect on chest pain. The senior FDA officials also were
told of sudden deaths in 142 other patients who took either Posicor
or a placebo in an ongoing study focused on congestive heart failure.
However, details from the 2,400-patient study remained sealed because
the manufacturer opposed breaking the experiment's confidentiality
until it was finished.
This left the FDA officials a choice: Wait a year or more, or
approve Posicor without knowing the details.
"I sure don't feel good about what I've seen," said Dr. Lemuel
A. Moye, a member of the FDA's Cardiovascular and Renal Drugs
Advisory Committee that met on Feb. 28, 1997. Moye, a physician and
biostatistician at the University of Texas, suggested it would be
prudent to delay judgment until the study's results were unsealed.
"I'm afraid that we are rushing into this."
According to a transcript of the meeting, Moye voiced concern
about Posicor's effect on heart rhythm and its potential to interact
with other compounds. "Patients will be taking this in fairly
uncontrolled situations in combinations of drugs which have
ramifications yet unknown," he said.
Another committee member, Dr. Robert Califf, professor of
medicine at Duke University, said: "If this [drug] was really
something that was dramatically different, better than anything else
in the way of relieving symptoms, then I would look at it
differently. But given the fact there are a lot of other effective
therapies out there, why not be safe with the public?"
Indeed, scores of other drugs for treating high blood pressure
were already on the market, and Posicor was not proved to offer
lifesaving benefit.
The drug's manufacturer, New Jersey-based Hoffman-La Roche Inc.,
saw no need to delay.
"There is no signal that there is arrhythmic or potentially
arrhythmic risk with the drug," said Roche's Dr. Isaac Kobrin,
terming the sudden deaths of four patients in another study "a chance
finding."
The committee voted, 5 to 3, to recommend approval of Posicor,
with Califf and Moye in the minority.
After presiding over the five-hour discussion, the committee
chairman, Dr. Barry M. Massie of San Francisco, abstained from voting
amid a financial conflict: Massie was a co-investigator in Roche's
ongoing study of Posicor. After that meeting, Roche hired him as a
speaker for the drug, Massie acknowledges.
On June 20, 1997, the FDA approved Posicor.
Four days later, a Roche news release quoted Massie to buttress
the company's claim that "the incidence of side effects was low"
during clinical studies of Posicor.
Asked about this sequence of events, Massie said, "You do wonder
how the world would perceive it. I'm glad I didn't vote, let's put it
that way."
Doctors were cautioned in speck-sized type--beginning on the
278th line of the drug's label and again on the 365th about
prescribing Posicor in combination with various medications,
including allergy pills, tranquilizers, a sleeping pill and the
heartburn drug Propulsid.
Authorities in Sweden in mid-1997 saw sufficient danger to keep
Posicor off the market. But the U.S. approval spurred high hopes for
Roche. Analysts at one brokerage firm, Salomon Smith Barney,
projected sales of $2.9 billion within four years.
Six months after approving Posicor, the FDA advised doctors of
the pill's "life-threatening" danger. The agency announced that it
had "received reports of dangerously lowered heart rates in about 20
patients." Roche agreed to a label change--advising that Posicor
should not be taken in combination with cholesterol-lowering drugs.
This brought to 26 the number of drugs that doctors were warned not
to prescribe with Posicor.
On June 8, 1998, Roche announced Posicor's withdrawal, citing
"evolving information concerning the potential for drug interactions"
and "preliminary results" from the ongoing heart failure study that
had drawn the attention of the advisory committee.
The study, Roche said, showed that the patients gained "no
overall" benefit from Posicor.
According to those familiar with the matter, the study also
found that the patients given Posicor died at a rate about 10%
greater than those who took a comparator. "It definitely did not look
good," recalled Fenichel, who was then the cardiac drug division's
deputy director.
Apart from the clinical research, records filed with the FDA
show that doctors and others reported Posicor as a suspect in the
deaths of 100 patients.
"Posicor should not have been approved," Moye said. "Therefore,
any death that was attributable to Posicor was an unnecessary death."
The FDA's Woodcock and Lumpkin wrote in their May 1999 medical
journal article that the problems that sunk Posicor also were
"unexpected." Asked recently about this, Woodcock retreated slightly;
she said that serious adverse reactions resulting from Posicor's
interaction with one drug "perhaps could have been anticipated."
Overall, she said, the agency had hoped for better compliance
with advice in the label to avoid the concomitant use of Posicor and
the 26 other drugs it interacted with.
A spokesman for Roche, Martin Hirsch, declined to answer
questions but said the company "demonstrated sound and responsible
judgment in the way [it] developed, launched and marketed and
withdrew Posicor. And we have cooperated with the FDA throughout."
_______________________________________________
Biofuel mailing list
Biofuel@sustainablelists.org
http://sustainablelists.org/mailman/listinfo/biofuel_sustainablelists.org
Biofuel at Journey to Forever:
http://journeytoforever.org/biofuel.html
Search the combined Biofuel and Biofuels-biz list archives (50,000 messages):
http://www.mail-archive.com/biofuel@sustainablelists.org/
