Healthy Skepticism Library item: 7143

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Publication type: news

End of Drug Trial Is a Big Loss for Pfizer
New York Times 2006 Dec 4
http://www.nytimes.com/2006/12/04/health/04pfizer.html?_r=3&th&emc=th&oref=slogin&oref=slogin&oref=slogin

Full text:

End of Drug Trial Is a Big Loss for Pfizer

http://www.nytimes.com/2006/12/04/health/04pfizer.html?_r=3&th&emc=th&oref=slogin&oref=slogin&oref=slogin

The news came to Pfizer’s chief scientist, Dr. John L. LaMattina, as he
was showering at 7 a.m. Saturday: the company’s most promising
experimental drug, intended to treat heart disease, actually caused an
increase in deaths and heart problems. Eighty-two people had died so far
in a clinical trial, versus 51 people in the same trial who had not
taken it.

Within hours, Pfizer, the world’s largest drug maker, told more than 100
trial investigators to stop giving patients the drug, called
torcetrapib. Shortly after 9 p.m. Saturday, Pfizer announced that it had
pulled the plug on the medicine entirely, turning the company’s nearly
$1 billion investment in it into a total loss.

The abrupt decision to discontinue torcetrapib was a shocking
disappointment for Pfizer and for people who suffer from heart disease.
The drug, which has been in development since the early 1990s, raises
so-called good cholesterol, and cardiologists had hoped it would reduce
the buildup of plaques in blood vessels that can cause heart attacks.
Just last Thursday, Pfizer’s chief executive, Jeffrey B. Kindler, said
publicly that the drug could be among the most important new
developments for heart disease in decades and that the company hoped to
get Food and Drug Administration approval for it in 2007.

“I’m terribly disappointed,” said Dr. Steven E. Nissen, chairman of
cardiovascular medicine at the Cleveland Clinic and lead investigator of
an earlier torcetrapib clinical trial. “This drug, if it worked, would
probably have been the largest-selling pharmaceutical in history.”

For people with heart disease, torcetrapib’s failure means that progress
may be slowing after two decades of substantial advances against the
disease. Medicines to lower blood pressure and bad cholesterol are
already effective and widely used, yet heart disease remains the biggest
cause of death in the United States, killing 911,000 people in 2003,
according to the American Heart Association.

Because the torcetrapib-related deaths occurred during a clinical trial,
before the drug reached the market, Pfizer will not face the product
liability lawsuits that have dogged Merck over its painkiller, Vioxx.
Merck withdrew Vioxx, a best-selling arthritis drug, after evidence
emerged that it could cause heart strokes and heart attacks. Patients in
clinical trials must sign waivers confirming that they understand the
risks they face when they take unapproved medicines in clinical trials.

Scientists had seen torcetrapib as the vanguard of a new wave of
medicines that would give physicians new ways to reduce heart disease by
raising good cholesterol, following the success of medicines called
statins, drugs like Lipitor that work by inhibiting the production of
so-called bad cholesterol. These drugs, which include Pfizer’s Lipitor,
are among the best-selling drugs in the world with tens of billions of
dollars in annual sales.

Now Pfizer, and independent cardiologists, must determine whether
torcetrapib’s failure indicates that all medicines to raise good
cholesterol will have similar problems, or if the problem was
specifically related to some defect in torcetrapib.

Pfizer had been three years into a late-phase clinical trial of
torcetrapib involving 15,000 patients when Dr. LaMattina, the Pfizer
scientist, fielded the call early on Saturday. Dr. Steven W. Ryder, a
senior Pfizer scientist overseeing the development of the company’s most
important experimental medicine, told Dr. LaMattina that the independent
researchers monitoring the torcetrapib trial – who were the only ones
privy to the results – had called Friday evening to recommend that it be
halted.

The independent monitors called regularly on the first of each month to
give a progress report. This time, however, the results stacked up
irretrievably against the drug’s safety, and the monitors had determined
that the numbers could not possibly reverse themselves in torcetrapib’s
favor.

Not only were there 31 more deaths among the people taking torcetrapib,
but similar discrepancies were seen in the number of patients suffering
heart failure and other problems, giving the company no choice but to
stop development.

Dr. LaMattina quickly called Jeffrey B. Kindler, Pfizer’s chief
executive, to tell him that the researchers thought the trial should be
stopped. By 8 a.m., Pfizer’s senior leaders were talking over the
results on a conference call.

Less than three hours later, the executives decided to stop the trial.
By Saturday afternoon, the company began to notify the 100 hospitals and
medical clinics on three continents that were running it. That night
Pfizer put out a press release announcing the news.

For Pfizer, torcetrapib represented a potential blockbuster medicine
that could generate several billion dollars in sales annually. Those
revenues are crucial for Pfizer, which is fighting to keep its revenues
from declining as it loses patent protection on best-selling drugs such
as Zoloft, an anti-depressant, and Zithromax, an antibiotic.

The problem comes at an especially bad time for the company, whose new
chief executive, Mr. Kindler, heavily promoted torcetrapib’s prospects,
most recently on Thursday at a conference for investors that Pfizer
hosted at its giant research center in Groton, Conn.

Pfizer shares, which have been among the worst-performing of any major
drug company over the last five years, will probably open sharply lower
today.

Pfizer, which has 106,000 employees and about $50 billion in annual
sales, is still highly profitable, but it will lose patent protection on
its best-selling drugs over the next five years. And despite a $7
billion annual research budget its near-term pipeline of new drugs is
nearly empty.

Pfizer’s decision to abandon torcetrapib throws into question the theory
that using drugs to raise good cholesterol, known as HDL, will benefit
patients. Some scientists worry that the drugs cause the body to produce
a form of HDL that may actually be harmful.The problem, though, could be
specifically related to a defect in torcetrapib, which is known to raise
blood pressure, a serious side effect for a heart medicine. Other
experimental drugs that raise good cholesterol, including two in very
early stage clinical development from Pfizer and another from Roche, do
not seem to have similar effects.

As is customary, Pfizer had hired a board of independent scientists to
monitor the torcetrapib trial, which had been scheduled to end in 2009.
The trial, called Illuminate, compared 7,500 patients taking a
combination of torcetrapib and Lipitor, Pfizer’s best-selling statin,
with a similar number of patients taking only Lipitor. The patients had
diabetes or cardiovascular disease, making them more likely to have
heart attacks or strokes than the general population.

Each month, the independent scientists reviewed data from the trial
comparing the effects of the two treatments. To protect the trial’s
integrity, people inside Pfizer were not allowed to see the data.

Pfizer had hoped the trial would show that people taking the combination
pill would be significantly less likely to suffer deaths or heart
problems than those taking Lipitor alone. Instead, it showed the opposite.

The Food and Drug Administration said it endorsed Pfizer’s decision to
end the trial and believed the company had acted properly. Torcetrapib’s
failure is disappointing, but developing new drugs is risky and
difficult, said Dr. Robert Meyer, director of the agency’s office of
drug evaluation.

“Research is research,” Dr. Meyer said. “If you knew the answer, you
wouldn’t be doing it.”

The discontinuation of torcetrapib is the second major failure in the
Pfizer’s development program in less than a week. On Tuesday, Pfizer
said it would no longer collaborate with Akzo Nobel, a European company,
on asenapine, a drug for schizophrenia.

Finding new medicines is crucial for Pfizer, which in 2004 began to lose
monopoly protection on several of its best-selling drugs, opening them
to cheap generic competition. In 2010, Pfizer faces the loss of patent
protection on Lipitor, the world’s top-selling medicine, with $13
billion in annual sales.

Michael Krensavage, an analyst at Raymond James, a financial services
firm, said that torcetrapib’s failure would force Pfizer to accelerate
its plans to lay off employees and reduce costs. “More job cuts are on
the way,” he said.

Mr. Kindler said he was surprised and disappointed at the findings.
Torcetrapib’s failure highlights the risks that drug makers face as they
try to develop new and important medicines, he said in a telephone
interview yesterday. “This is a very high-risk business,” he said.

Still, the company is financially strong and expects to report higher
profit in both 2007 and 2008, mainly due to cost-cutting, Mr. Kindler said.

Dr. Meyer of the F.D.A. said that torcetrapib’s failure did not mean
that similar medicines under developed should be abandoned.

“If another drug raised HDL but didn’t affect blood pressure, that might
be suitable,” Dr Meyer said. “The finding certainly raises concerns and
would make everybody appropriately cautious, but it’s not enough to say
this class is at a dead end.”