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.