Papers Indicate
Bayer Knew of Dangers of Cholesterol Drug
By MELODY PETERSEN and ALEX BERENSON
February 27, 2003
Newly disclosed company documents
indicate that some senior executives at Bayer
were aware that their anti-cholesterol drug had serious problems
long before the company pulled it from the market.
The documents, made public by
lawyers suing Bayer, include e-mail messages, memos and sworn
depositions of executives that suggest that Bayer promoted the
drug, Baycol, even as a company analysis found that patients on
Baycol were falling ill or dying from a rare muscle condition much
more often than patients on similar drugs.
The lawyers are suing Bayer,
which is based in Germany, and its British marketing partner, GlaxoSmithKline,
in federal court in Minneapolis and in dozens of other cases
around the country. Though the documents do not paint a full
picture of what the companies knew, or how early they knew it
before Baycol was pulled from the market in 2001, they provide a
rare glimpse inside a major drug company's marketing efforts in
the face of mounting indications of trouble.
Bayer, which developed Baycol,
says the drug was marketed appropriately and is safe when used
properly.
But approximately 100 deaths and
1,600 injuries worldwide have been linked to a muscle disorder
caused by the drug, according to regulatory filings by the
company. Similar drugs are at least as effective as Baycol but
cause the disorder much less frequently, according to the Food and
Drug Administration.
The F.D.A., which allowed the
sale of two higher doses of Baycol in the years after initially
approving the drug, said it did not see a rapid increase in deaths
until the spring of 2001, and Bayer took the drug off the market
shortly after the agency raised serious concerns about it with
company executives in late July.
The drug, which studies found to
be less effective at its initially approved strength than
competing medicines, caused more problems at higher doses. Senior
executives at Bayer and GlaxoSmithKline were aware that this might
be possible as early as 1997, according to a letter that is part
of the court filings.
Philip S. Beck, a lawyer with
Bartlit Beck Herman Palenchar & Scott, who is representing
Bayer, said the company monitored reports on Baycol from doctors,
shared those reports with regulators and repeatedly added to the
written warnings on the drug's label. "We did what companies
should do," he said.
Patricia Seif, a spokeswoman for
GlaxoSmithKline, said the company's "promotion of Baycol was
fully consistent with the product label that the F.D.A.
approved."
More than 10,000 patients who
took Baycol or the families of those who died have filed lawsuits
against Bayer and GlaxoSmithKline. The first trial, in Corpus
Christi, Tex., began Tuesday.
Bayer and GlaxoSmithKline have
settled more than 400 of the cases for individual amounts ranging
from $200,000 to $1.2 million, according to lawyers for the
patients. At that rate, the drug makers could pay billions of
dollars to resolve all the lawsuits. The companies deny the
allegations in the lawsuits, and Bayer says that no more than 15
percent of the patients who have sued actually suffered any injury
and that it is trying to settle most of those claims. Lawyers for
the plaintiffs dispute that estimate.
The companies have agreed that
Bayer, which discovered the drug and played the biggest role in
marketing it, will pay 95 percent of the cost of settling cases.
Mr. Beck said that the company
still believed that Baycol was safe when prescribed according to
the instructions and warnings in its label. Bayer took the drug
off the market, he said, because doctors were not using it as
directed by the label.
The company was also being
pressured by the F.D.A. The agency had allowed Bayer to sell
higher doses of Baycol because it did not notice unusual rates of
complications from the drug. But Dr. David G. Orloff, director of
the F.D.A. division that reviewed Baycol, said that in the spring
of 2001, less than a year after approving a higher dosage of
Baycol, the agency noticed a sharp jump in reports of deaths and
serious injuries in patients using Baycol, and after investigating
the reports it pressed Bayer to pull the drug. "It took time
and tragedy to understand it was different," he said.
The drug makers have demanded
that many documents in the cases remain sealed, and judges have
acceded to the request. The documents that have become public have
been introduced in court by lawyers for plaintiffs trying to
broaden the lawsuit against Bayer and seek additional damages. The
available documents show how the companies responded as they
received reports of a dangerous side effect called rhabdomyolysis,
which causes muscle cells to break down and their contents to flow
into the blood.
Even mild cases of rhabdo, as
doctors commonly call the condition, can cause severe pain and
muscle weakness. In more serious cases, rhabdo can cause paralysis
or death as the kidneys shut down.
John Nahay, 71, said he
"just got weaker and weaker" after beginning to take
Baycol in the summer of 2001, shortly before it was pulled from
the market. Mr. Nahay, who lives in Langhorne, Pa., and is among
the thousands who have sued Bayer, must now undergo dialysis
treatments three times a week and is largely confined to his
house. "It's hard to believe that that little pill could do
that," he said.
Regulators approved Baycol in
June 1997, making it the sixth of a group of popular cholesterol
reducers called statins. By August 2001, when Baycol was removed
from the market, at least six million people worldwide had taken
the drug, including 700,000 Americans, according to Bayer. With
sales that year expected to exceed $600 million, it had become one
of the company's fastest-growing products.
But on June 27, 1997, the day
after Baycol was approved by the Food and Drug Administration,
Jerry Karabelas, executive vice president for pharmaceuticals at
SmithKline Beecham, which later merged with Glaxo, wrote to David
Ebsworth, president of Bayer's North American pharmaceutical
operations, saying he had "serious concerns" about using
the drug with some other medicines, according to excerpts of the
letter included in court papers.
Mr. Karabelas said that Baycol
appeared to be no stronger than a competing drug called Lescol.
But, he said, Baycol also caused "drug interactions that
could be magnified at higher doses."
"Simple and safe," Mr.
Karabelas wrote, "no longer appears to be a viable
promotional platform."
Fred T. Magaziner, a lawyer with
the Dechert law firm that is representing GlaxoSmithKline, said
that Mr. Karabelas was writing about drug interactions that were
later proved not to be a problem with Baycol.
Still, the e-mail message
indicates that some top executives had concerns about the drug's
safety early on.
Bayer began marketing Baycol in
early 1998, and doctors soon began reporting serious side effects.
In April 1999, Dr. William Pogson, a cardiologist in Independence,
Mo., wrote in The American Journal of Cardiology that a patient
had developed "profound muscle weakness, and the inability to
walk" in September 1998 after taking Baycol for three weeks
alongside Lopid, another type of cholesterol drug. A few months
later, a second patient of his developed rhabdomyolysis while
taking Baycol, but not Lopid. "It made me want to stay away
from the drug," Dr. Pogson said in an interview.
Nonetheless, the F.D.A. approved
a stronger dosage of 0.4 milligram of Baycol in May 1999.
That October the F.D.A. expressed
its first public concerns about Bayer's marketing, warning the
company in a letter that its sales materials were "false,
lacking in fair balance or otherwise misleading" and that
they underplayed "the most important risk information"
on rhabdomyolysis.
Mr. Beck said the warning was
isolated and similar to dozens of others received by drug
companies, including the makers of other anti-cholesterol drugs.
In December 1999, Bayer added a
warning to the drug's label saying that Baycol should not be
prescribed with Lopid — a warning stronger than those on the
labels of similar drugs. A drug's label, which is approved by the
F.D.A., is a document included in a drug's package that often
spans many pages, and doctors rely on these labels when they
prescribe medicines.
Some Bayer executives, however,
were aware that doctors might ignore the label change. In August
2000, Laurie Simpson, a manager in Bayer's strategic analysis
division, wrote to Tig Conger, vice president for cardiovascular
and metabolic marketing, saying, "If the physician's
experience is that he/she has safely used combinations in the
past, tendency would be to discount the contraindication."
Mr. Beck, Bayer's lawyer, said
the warning about drug combinations was emphasized in all sales
material.
As the drug became more widely
used, more doctors reported problems. In April 2000, three Spanish
doctors reported in The Annals of Internal Medicine a case of
rhabdo in a woman who had taken Baycol but not Lopid.
At the same time, Bayer was
preparing to introduce another new, higher dosage of Baycol. At
least one health official of the company expressed concerns about
the new stronger version.
In May 2000, when Bayer was
anticipating F.D.A. approval of the stronger version of Baycol in
July, Dr. Richard Goodstein, vice president for scientific
relations at Bayer, sent an e-mail message to Patricia Stenger, a
manager in Bayer's scientific affairs division, about a meeting of
the "Baycol Project team." Dr. Goodstein told Ms.
Stenger that he saw "a false comfort factor in place across
the company" about the drug.
Reached at her home, Ms. Stenger
said she could not comment. Dr. Goodstein did not return telephone
calls, but Mr. Beck said Dr. Goodstein was concerned about Bayer's
reputation in the medical community and not about Baycol's safety.
"With the stronger medicine
there is always a chance of more adverse reactions," Mr. Beck
said, "but some people need the stronger medicine." He
said that Bayer warned doctors of the risks of the higher dose but
believed that it could be safely prescribed.
The new tablet was approved by
the Food and Drug Administration in July 2000. The label on the
new 0.8 milligram tablets stated that doctors should start
patients on a lower dose.
At the same time, reports of
problems were increasing. In an August 2000 article in the journal
Angiology, Turkish doctors reported a death after a patient took
Baycol and Lopid.
That November, Bayer analyzed
reports of side effects and found that patients taking Baycol
alone had 5 to 10 times the chance of developing rhabdo as
patients on the other medicines.
Mr. Beck said Bayer then hired
Pacificare, a managed care company, to more thoroughly analyze
Baycol's risks among its members. The study did not include
patients taking the highest dose of Baycol. It found that the drug
at lower doses was no more risky than other statins as long as it
was prescribed according to the label directions, Mr. Beck said.
Still, the reports of problems
with Baycol continued. In December 2000, the Harris County public
hospital system in Houston stopped using Baycol after seeing six
cases of rhabdo in just nine months in patients taking the drug.
The increase in rhabdo cases "was a noticeable thing in a
hospital system our size," said Dr. David Hyman, chief of
general internal medicine at Ben Taub General Hospital in Houston.
"We made a decision we were uncomfortable with the
drug."
Eight months later, in August
2001, Bayer pulled Baycol from the market.
|
