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6 July 2005, The Wall Street Journal
A14
(Copyright (c) 2005, Dow Jones
& Company, Inc.)
Many observers -- including some on Congressional
oversight committees -- are still puzzled by the Food
and Drug Administration's recent decision to effectively
pull a good lung cancer treatment called Iressa from
the U.S. market. Let us suggest that the best way to
look at it is as an all-too-predictable case of bureaucratic
revenge.
Forgive us for getting personal, but in this case the
personal is the political is the policy. FDA oncology
drugs chief Richard Pazdur is the most important person
in the U.S. government when it comes to cancer drugs,
and he has never made a secret that he dislikes the
accelerated approval process under which Iressa got
the green light. Nor has he been shy about suggesting
that the agency was railroaded in this drug's case.
The truth is that Iressa-maker AstraZeneca
simply refused to play by Dr. Pazdur's rules. In 2002
-- knowing it had plenty of data to qualify for accelerated
approval -- the company rebuffed his requests for more
trials and appealed directly to something called the
Oncologic Drugs Advisory Committee (ODAC).
That September, the practicing cancer
doctors on ODAC agreed with AstraZeneca, voting 11-3
to recommend Iressa's approval. "Ten percent [response]
is pretty substantial," remarked ODAC chairwoman
Donna Przepiorka. "I've never seen a lung cancer
patient whose cancer went away by itself. Very clearly
there are patients whose cancer went away with Iressa."
Dr. Pazdur tried his best to find reasons to reject
the ODAC recommendation, but eventually the FDA relented,
granting approval in May 2003.
What's changed since? Not much about the
data on Iressa's effectiveness. We still know it helps
only about 10% of lung victims -- nothing to sneeze
at for such a deadly cancer. There is now even a genetic
test to help predict in advance which patients will
respond.
What has changed is the politics. For starters, Dr.
Pazdur no longer labors under the reform-minded former
FDA Commissioner Mark McClellan. Dr. Pazdur has also
since stacked ODAC with people who share his anti-industry
views. Most importantly, the unrelated panic over painkiller
safety last fall has created the political cover for
Dr. Pazdur to punish AstraZeneca for disobeying his
wishes.
Some readers may find it hard to believe
that life and death decisions about drug approvals and
withdrawals would be made for political reasons. So
it's worth pointing out that Dr. Pazdur has admitted
doing so before. In 2002, the FDA rejected Erbitux,
with Dr. Pazdur admitting it was a "good drug"
but that it had a "bad development plan."
Erbitux later became a clinical success against colon
cancer.
But later that same year when the FDA
approved a colon cancer chemotherapy called Eloxatin,
Dr. Pazdur approvingly remarked "we want to send
a message" about "the value in doing randomized
trials." In other words, the less revolutionary
drug (Eloxatin) got approved first because its makers
had jumped through the right bureaucratic hoops.
The Iressa move is Dr. Pazdur's way of
sending another "message" about the necessity
of doing things his way. It isn't so much a withdrawal
as a relabeling of the product. Patients currently on
the drug will be able to continue with it. But come
September no new patients will be able to start on it
outside FDA-approved clinical trials. In other words,
the option to use Iressa freely as a front-line cancer
treatment will disappear.
That prospect doesn't sit well with patients
like Sandy Britt, who believes Iressa saved her life
after she was diagnosed with metastatic, stage 4 lung
cancer late last year. "The first doctor gave me
a death sentence," the 46-year Alameda, California,
resident tells us. "She wasn't even going to treat
me." But another doctor administered a genetic
test that indicated she would be one of the 10% who
respond to Iressa. "I've had an amazing response
to it. They predicted I'd be dead now. Instead, I just
got back from three weeks in Italy." As for Dr.
Pazdur's decision, Ms. Britt asks a common-sense question:
"This is a drug that works amazingly well for some
people, so why take it off the market?"
The only possible excuse is that there
is now an alternative non-chemo lung-cancer treatment
called Tarceva with marginally better clinical-trial
results. But remember that such results are only averages
for the population, and that the responses of individual
patients differ widely. Dr. Pazdur's decision to give
future cancer patients -- even those with the Iressa-response
gene -- only the option of Tarceva could well amount
to a death sentence for many. Dr. Bruce Johnson of the
Dana-Farber Cancer Institute points out that there is
little data supporting the efficacy of Tarceva in patients
who have the mutation for which Iressa is believed to
be effective.
Dr. Pazdur and his allies like to suggest
that accelerated-approval advocates risk throwing science
out the window. But in truth, there's no scientific
reason to believe that large placebo-controlled trials
-- in which treatments are tested against nothing, i.e.,
the proverbial sugar pill -- should be considered the
"gold standard," as Dr. Pazdur believes. Withholding
treatment is unethical in terminal diseases, and we
have enough historical data about how cancer patients
fare to judge new treatments without the need for placebo
control groups.
This was the philosophy that the practicing
doctors of ODAC implicitly endorsed when they approved
Iressa; it was the philosophy promoted by former Commissioner
McClellan; and it is the philosophy that Dr. Pazdur
and his fellow FDA bureaucrats are challenging by pulling
Iressa now that there is a politically opportune moment
for them to do so. Never since the creation of the accelerated
approval process in 1992 have the regulatory barriers
to cancer research looked so oppressive.
(Copyright (c)
2005, Dow Jones & Company, Inc.)
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