From the Wall Street Journal, April 3 2002

FDA Trials Cost Lives

By ROBERT OLDHAM

Non-Hodgkins lymphoma (NHL) is an increasingly frequent, incurable
cancer of the lymph nodes which often spreads to other organs.
Approximately 54,000 Americans will be diagnosed with NHL this year,
and as many as 25,000 will die from it. NHL is one of the most
frequent killers of 20-to-39-year-old men. A subset of NHL called
follicular lymphoma has an average survival time of some seven to
eight years but is ultimately incurable, resulting in 4,000 to 5,000
deaths each year. That's the bad news.

The good news is that new biologically based, personalized
treatments, rather than one-size-fits-all chemotherapy, have an
excellent likelihood of effectively treating this cancer -- to the
point of possibly curing follicular lymphoma.

Sounds promising, so what's the problem? The problem is the Food and
Drug Administration, the agency that approves all new cancer
treatments. If the FDA applies its usual standard of a randomized
clinical trial to prove "once and for all" that this new treatment
works, it will not be available to all NHL patients who need it;
thousands will die while the FDA awaits proof of its efficacy.

Sadly, this isn't unique to NHL. For all our medical advancements, we
seem to accept the notion that needless deaths must occur to bring a
promising new treatment to those in need. This simply isn't the case.
In fact, there are many ways our drug development methods and the FDA
could be made more efficient. A closer examination of NHL and its
treatment will help to illustrate this point.

Lymphomas are composed of cells called lymphocytes, which in their
normal state are part of our immune system, helping the body fight
infection and cancer. Each begins as a single cell "gone bad," which
through growth and reproduction ultimately becomes a mass of cells we
call lymphoma. Since all the cancer is from one cell and since
lymphocytes have the property of expressing a unique protein on their
surface, called an "idiotype," we have a specific cancer marker or
target to attack.

For 30 years, scientists have been studying this target, and making
antibodies against it -- so-called anti-idiotype antibodies. In 1999,
a landmark study of a cancer vaccine demonstrated that 90% of the 22
NHL patients who received it had long remissions, and 77% were in
remission up to 74 months post treatment (as of 2001). This therapy
yielded "molecular remissions," never seen with chemotherapy alone,
where the cancer cell bearing the idiotype was completely eliminated
as determined by the most sensitive test now available. This vaccine
uses the idiotype protein to immunize patients against their own
cancer, in effect using their own cancer cells to effectively treat
and possibly cure their cancer.

Given the encouraging, long-term results of this study and others,
the National Cancer Institute -- with FDA guidance and consent -- is
now planning an extensive, five-year, random clinical trial of the
vaccine. The trial will include 563 patients; half will receive the
active vaccine and half a vaccine with no known activity in lymphoma
patients. Not only will 282 participants in the trial be denied the
active vaccine, 4,000 NHL patients will die each year during the
study without ever having the opportunity to try the vaccine.

This sort of study is not only unfair, it's outdated. It simply does
not make ethical or scientific sense to apply a drug development
paradigm developed decades ago for drugs designed for large
populations of patients to these new, personalized medicines
developed from the patient's own tissues. A better alternative would
be to allow these individualized cancer therapies to be prepared by
biotechnology companies under the guidance of experienced
oncologists. One could then judge their long-term effectiveness by
standard clinical means, such as comparing results to patients
treated concomitantly or in the past with other therapies.

Randomized trials are essential in the search for minor variations in
patient response to treatments. But when major improvements in
treatment exist and can be made available, it is neither reasonable
nor ethical to carry out such studies. Ask any patient, would you
rather have chemotherapy alone with an assured fatal outcome, or
would you rather receive chemotherapy plus a personalized vaccine
where at least 50% of the patients will be alive and in remission
five years later?

The new FDA commissioner -- whoever it is -- should immediately
change procedures or ask for legislation to encourage the more rapid
development and approval of personalized therapies to those in peril.
We must calculate the lives lost and improve the system so these new,
less toxic, more effective, personal medicines can be made available
now.

Dr. Oldham is chairman of the South Carolina Biotechnology
Association and CEO of Cancer Therapeutics Inc.

Updated April 3, 2002