May 11, 2007

Dr. Andrew von Eschenbach
Commissioner, FDA
5600 Fishers Lane
Rockville, MD 20857

Subject: FDA Decision Regarding Provenge

Dear Dr. von Eschenbach,

I am usually not one to write letters to decision makers in our
Government, though I served as a civil servant myself at NASA for
32 years. I do have, however, a sense of a public servant’s
responsibility to the American people whom I served. As a civil
servant and the appointed leader of the FDA, charged with
promoting the well being of Americans with respect to foods and
drugs, I need to request that you explain to the people and their
medical doctors why you chose not to approve Provenge, even
though you were advised by your appointed panel of Oncologists,
Urologists, and Immunologists, all experts in the fields of
immunotherapy and oncology, that Provenge is unquestionably safe
(100% of the experts voted yes on safety) and that there was
“substantial evidence” of the drug’s effectiveness as required by
FDA regulations (76% of the experts voted yes on substantial
evince of effectiveness). I must add that two of the no votes on
efficacy came from two doctors who have conflicts of interest
that your agency recognized before appointing them to the panel,
and I must ask if they would have even been allowed to
participate on the Provenge panel if FDA were now following its
new guidelines on conflicts of interest? If no, then the vote
without them would have been 13 to 2, or 86% in favor with regard
to substantial evidence of effectiveness. I include these
percentages since I know FDA is always very interested in
statistics!

In walking away from the advisory panel votes on Provenge, I and
the rest of older men who expect do battle with PC, would like a
detailed public and scientific explanation of your decision.
Certainly FDA has approved drugs against the recommendations of
its advisory panel, but I am not aware of a decision to overrule
a strong positive panel vote for a terminal illness that has no
really acceptable treatment options. This decision would appear
to be unprecedented, and calls for a full and open public
statement of why the FDA disagrees with this panel and cannot
make this drug available to terminal patients. We know of course
it was not due to safety concerns. Also, if FDA found the
clinical trial data submitted by Dendreon to be insufficient, why
did you even submit the data to a panel of experts for their
opinions? This suggests the worst sort of scientific arrogance on
the part of FDA regulators, or worse.

Let me offer several other reasons why a detailed public
statement from you and your personal involvement to achieve a
resolution is absolutely critical at this time. You have made
many public promises that FDA would be a “bridge builder” and not
a barrier. You could have built a bridge with Provenge by
approving it with a post-marketing trial requirements, and
allowing combination trials to be initiated with other treatments
such as Taxotere. For example, Dr. Petrylak’s analysis in The
Urology Times pointed to a staggering survival benefit when
Provenge is used with Taxotere. In fact, a 14-month survival
advantage when compared to Taxotere alone. Surely you were
informed of Dr. Petrylak’s analysis? And then there is the
Dendreon P-11 trial with early stage PC patients, showing a
remarkable and clinically significant increase in PSA doubling
time exceeding 40%. Surely FDA was told about this clinically
significant benefit, were they not? Dr. von Eschenbach, the FDA
said they wanted to see more data. How much is enough? Would you
be turning away from this kind of data if the disease were breast
cancer, instead of prostate cancer? Would you?

Dr. von Eschenbach, this decision by FDA can be, if you decide to
do so, a bridge-building event. The credibility of FDA with the
medical world is at stake here. You can build a bridge by being
flexible with Dendreon as to additional data required for
approval. Do something constructive here and do it quickly. Call
in Dr. Petrylak, the Taxotere Principal Investigator, and those
members of the AC panel who can serve now. Have the company
present all of its existing trial data from other trials as well
as those submitted thus far. Allow the company to un-blind the
on-going 9902b trial data to examine with you the TTP evidence
using updated immunotherapy parameters instead of the outdated
chemotherapy parameters that caused the TTP in the first Provenge
trial to barely miss statistical significance, and “work with”
this company to bring Provenge to market this year. Please don’t
walk away from this for several more years as we wait for the
statistical picture to become more complete. It will never become
a certainty. It will always be a probability. Your own
statistician said the chance that the observed survival benefit
in the completed trials occurring by chance and not by Provenge
was only 1 in 50. Is this not enough to give you a reasonable
comfort level sufficient to give Provenge to the 80,000 men who
will die over the course of the next few years?

You have also told the medical research community that FDA would
work to reduce the time and expense to bring new drugs to
approval. Surely this must apply to Provenge, a treament for
terminally ill cancer patients who have little time to live. Dr.
von Eschenbach, do what you promised to do.
“TEAR DOWN THIS WALL!”

Be the leader we thought you to be. Be courageous. If you need to
overrule ODAC and the chemo lobby, then do it. We have no
champion but you. We have no voice but yours. Ronald Reagan did
it in Berlin. You can do it in Washington.

Will you do the morally right thing and bring this first cancer
immunotherapy to the people, even though your understanding of
the science is less than perfect? Review again the transcript of
the March 29 meeting. Dr. Marincola and Dr. Pensen, who spoke
from the public pulpit, urged you to consider the effect of your
decision on cancer research. As did others at that table. You
also have promised to encourage, not kill, cancer
immunotherapies. Do what you promised, and talk to those on the
panel who urged FDA to approve Provenge now so new trials could
go forward. FDA desperately needs to understand that they must
become partners with small biotech companies that cannot go on
spending hundreds of millions of dollars to perfect the trial
data beyond any shadow of a doubt. There is no unlimited source
of funds. The law calls for substantial evidence, not absolute
proof, of efficacy.

Become a partner with those whom you promised to serve , and
those who depend on your cooperation as a regulator – the
research community. These companies’ scientists are giving their
lives to save others. Surely you can give them your support. We
are counting on you…..

God Bless You and Your Staff,

Joseph Sperty
2011 S Conference Dr.
Boca Raton, FL 33486

Cc: Jesse Goodman, M.D., Director, CBER
Celia Witten, M.D., PhD., Director, Office of Cellular, Tissue
and Gene Therapies