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"Cancer Regression"
By RICHARD MILLER
August 1, 2007; Page A15

The most welcome news a cancer patient can hear from their doctor
is: "Your tumor is regressing." Sadly, the message that the Food
and Drug Administration is now delivering to cancer patients is
that the fight against tumors is regressing.

Current FDA policies are discouraging the development of
groundbreaking treatments for cancer and other killer diseases,
turning the clock back on hard-won regulations put in place in
response to the AIDS crisis that allow patients faster access to
new drugs. Case in point: This week, facing rejection by the
Agency, GPC Biotech withdrew its New Drug Application (NDA) for
Satraplatin, a drug to treat prostate cancer -- despite data from
a large controlled clinical trial showing the drug delayed tumor
growth in patients where the disease is widespread.

Most of the patients in this study had exhausted all known
therapies; many required powerful medication to control bone
pain. Time is running out for them, yet results from this
statistically significant study were not sufficient for the FDA.
Although GPC Biotech's application for Satraplatin was under
consideration for accelerated approval, the Agency indicated it
would need to wait for full survival data from this trial, which
will delay approval at least one year.

Sadly, far from being an aberration, Satraplatin is the fifth
promising cancer treatment set back by the FDA this year. In May,
the Agency sparked a firestorm of patient protests when it
disregarded the overwhelmingly positive recommendation of an
outside advisory panel and turned thumbs down on Provenge, a
revolutionary "vaccine" designed to extend the lives of patients
with advanced prostate cancer by stimulating their immune
systems.

More quietly, the Agency also turned thumbs down on Junovan, a
vaccine for pediatric bone cancer; orBec, to treat leukemia
patients who have received bone marrow transplants; and my own
company's Xcytrin, to treat lung cancer that has spread to the
brain.

In each case, the FDA overlooked substantial evidence of the
drug's positive impact in slowing the progression of killer
cancers and improving quality of life -- evidence that should
have been at least sufficient to warrant conditional approvals
under established regulations that have been eroded by the
Agency's bureaucratic intransigence.

The Junovan rejection is particularly heartbreaking because now
we'll probably never know if this vaccine could have helped
children with bone cancer. Due to the rarity and complexity of
the disease, it is extremely unlikely that this vaccine will be
tested again for this condition.

This is not the way the regulatory system is supposed to work for
patients with life-threatening diseases such as AIDS, cancer and
Alzheimer's. Thanks in large part to AIDS activism, Congress
passed legislation that in 1992 resulted in new regulations that
streamlined the approval process for drugs intended to treat
life-threatening diseases. One such regulation, accelerated
approval, gave desperately needy patients faster access to new
drugs. It allows for conditional approval based on data
"reasonably likely" to predict clinical benefit while more
definitive trials are being conducted.

The idea worked: 26 new cancer drugs for 30 different clinical
indications were approved between 1995 and 2005 under the
accelerated approval regulation. Important drugs such as
Camptosar, Eloxitan, Gleevec, Temodar and others were made
available to patients more quickly than under the standard
approval procedures. Thousands of patients benefited from faster
access, and these drugs went on to find vital and expanded roles
for the treatment of many types of cancer.

There appears to be no evidence that any harm was done by
accelerating the approval process for these products. Indirectly,
the streamlined review and approval process has also stimulated
the pharmaceutical industry to invest in the development of new
drugs for these diseases.

In recent years, the FDA has effectively regressed to a pre-AIDS
mindset. The accelerated approval requirements have stiffened and
the real benefits of the process for patients have been whittled
away. Since 2005, only one drug has achieved accelerated approval
and this year none have been able to break through the FDA's iron
gate.

The first step backward was requiring that sponsors submit a
protocol for the planned confirmatory trial before conditional
approval could be granted. Then came a requirement that patient
enrollment must first be initiated in the confirmatory trial,
then a requirement that all patients be fully enrolled in the
trial. With Satraplatin, we have reached the tragic, logical
conclusion of this process: The FDA has decided it would prefer
to wait for the final data from the confirmatory trial before
granting "accelerated approval," making a mockery of the term and
effectively killing the whole concept behind it.

Things have not always been this way at the FDA. In 1983, I
cofounded IDEC Pharmaceuticals to develop the then-novel concept
of antibodies for treatment of cancers of the immune system or
lymphomas. Fortunately, based on a relatively small study, IDEC
gained approval in 1997 for a drug we discovered five years
earlier called rituximab. It is now widely used for the treatment
of most lymphomas and several autoimmune diseases such as
rheumatoid arthritis. I highly doubt that this relatively short
period from discovery to market could have occurred in today's
regulatory environment. As a consequence, antibody therapy and
its benefits for thousands of patients never would have been made
available.

For patients with life-threatening diseases and their families,
the implications of the FDA's recent regressive trend are
devastating. It may be acceptable for regulators to be
risk-averse when considering drugs for routine or nonserious
diseases where alternative therapies exist. But this mindset is
simply irrational when it comes to drugs intended to treat
patients suffering from deadly diseases -- people who often have
only weeks or months to live.

Clearly we need to get back to a more context-sensitive
regulatory approach for reviewing drugs targeting deadly
diseases. That is not to say that rigorous scientific principles
should be abandoned. But in medicine, ethical and practical
considerations have to play a role too.

Congress should require the FDA to follow the existing
regulations on accelerated approval. Only then will we be able to
make the progress we need in the fight against killer diseases
like cancer.

Dr. Miller is president and CEO of Pharmacyclics, and adjunct
professor of oncology at Stanford University Medical Center.