Black Wednesday at the FDA
By MARK THORNTON
May 14, 2007

May 9, 2007, should be cited in the annals of cancer immunotherapy as Black Wednesday. Within
an eight-hour period that day, the FDA succeeded in killing not one but two safe, promising
therapies designed and developed to act by stimulating a patient's immune system against
cancer. The FDA's hubris will affect the lives and possibly the life spans of cancer patients
from nearly every demographic, from elderly men with prostate cancer to young children with the
rarest of bone cancers.

The dream of stimulating a person's immune system to fight his cancer is older than the modern
era of cancer chemotherapy. Over a hundred years ago, Dr. William Coley at Memorial Hospital in
New York City experimented with bacterial agents that appeared to have properties in
stimulating immune responses against sarcoma, a cancer of the muscles and bones. Advances ebbed
during the era of chemotherapy in the mid-20th century, but over the last 25 years cancer
immunotherapy has received much research focus and periodic support from the biotechnology
industry.

Progress and investment, however, have been unsteady as tumor shrinkages following treatment
never quite translated into "hard," clinically relevant outcomes such as prolongation of the
survival of the patient. Still, this type of approach remains the Holy Grail of cancer
treatment. One day current treatment approaches such as surgery, radiation and chemotherapy,
which often kill most but not all of a cancer, could be made obsolete by a potent immune
response that eradicates the cancer cells and provides subsequent protection against return and
relapse.

Thus it was remarkable that in the last several months two different biotech companies, with
products utilizing two completely different cancer immune approaches, came before the FDA's
Advisory Committee Meeting for judgment. The first product, Provenge, made by the Dendreon
company, is a cellular therapy that tackles prostate cancer. The results of the Provenge
clinical trial in men with prostate cancer who had failed all other therapies appeared before
the committee that advises on cell-based cancer products for the FDA Center for Biologics. This
committee was comprised of immunology and oncology experts. The second product, Junovan, made
by the IDM company, was tested in children with osteosarcoma, a rare bone cancer that affects
just 900 children per year. The results of the Junovan clinical trial appeared before a
different committee -- one that judges protein cancer agents and was comprised solely of
oncologists with no immunology experts.

Both the Provenge and Junovan clinical trials provided evidence that patients lived longer
compared to control groups. But according to the FDA, these "survival advantages" that
statisticians talk about had "issues." When the issues were discussed in the Provenge public
meeting the majority of the committee (in a 13-4 vote) thought the issues, while relevant and
important, were superseded by the solid immunology science behind the product.

However, those voting in the minority, very powerful members of the oncology community,
launched an unprecedented PR campaign accusing those in the majority of incompetence and
naiveté in matters relating to cancer products. The arrogance of this campaign overlooked the
notion that survival data from immune-based products may be qualitatively different from, and
may need to be judged by different criteria than, survival data from chemotherapy drugs.

But such intriguing academic discussions never had a chance to take root. Instead -- just a few
weeks after the favorable ruling on Provenge -- the Junovan product came before the FDA's
Advisory Committee for approval. Incredibly, the improvement in the survival rate of children
with bone cancer who received Junovan was summarily dismissed as irrelevant by the committee.
Why? The statistical data showing the odds of efficacy were 94% surety instead of the usual
goal of 95% surety. This 1% difference was all the committee needed to justify a 12-2 "No"
vote.

The Junovan meeting was chaired by the very physician who launched the PR campaign against
Provenge. Unlike the meeting on Provenge, however, all discussion time on Junovan was spent
kneeling before the altar of statistics -- not a single comment was made about the immunology
science supporting the efficacy of Junovan. Remarkably, as the Junovan vote was taking place,
the FDA folded under the pressure and announced that it would not abide by the favorable vote
on Provenge. Instead, the FDA called for more testing that -- if the product is not killed
outright by its maker Dendreon -- will take at least three years to complete.

In the span of eight hours, the dawn of a new era in cancer immunotherapy was driven back into
the night. It will be years before we know the full impact of these decisions and how many
cancer patients, young and old, have had their lives cut short as a result. For now, however,
one thing is clear: While our lawmakers obsess over FDA "safety reforms," no one is holding
this government agency accountable for its complicity in stalling therapies for
life-threatening diseases.

Dr. Thornton, a former medical officer in the FDA Office of Oncology Products, volunteers as
president of the Sarcoma Foundation of America.

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