By Sarah Yang, San Francisco Examiner
SAN FRANCISCO-- Countless numbers of terminally ill patients in
the United States wage life-and-death battles to gain access to
experimental drugs available largely to people in clinical trials.
Whether they can -- or should -- get special access to these drugs is
a subject of huge debate.
One such patient is Larry Williamson, 52, who was diagnosed in
July with kidney cancer, which had spread to other parts of his
body and was growing rapidly. A tumor undetected in tests two
months earlier was the size of a tennis ball. His doctor said he
had anywhere from two to eight months to live.
Williamson has pinned his hopes on anti-VEGF, an experimental
drug that has not been approved for market by the Food and Drug
Administration.
``I thought, if there's any chance that something might save my
life, how will I feel if I'm facing death and I haven't tried to
get it,'' said Williamson, who lives in San Francisco. ``I just
want to know I exhausted all the possibilities for extending my
life.''
Williamson had tried chemotherapy. It hadn't worked; it rarely
does for renal cell carcinoma. A newer treatment, interleukin-2,
failed as well. It does so in four out of five kidney cancer
patients.
The FDA makes room for such last-resort cases under ``expanded
access'' programs, allowing seriously ill and dying patients with
no real alternative the chance to take a drug before it is approved
by federal regulators.
Such programs were broadened in the 1980s in response to demands
from AIDS activists for greater and faster access to new
medications. Since then, tens of thousands of patients have
received access to drugs treating such illnesses as heart disease,
AIDS and cancer.
According to some specialists, expanded access programs have
become more popular in recent years as more patients use the
Internet to find out about new drugs under development.
Ultimately, however, it is the manufacturer -- which absorbs the
cost of supplying the treatment before market approval -- that must
weigh the burden of providing expanded access against the
desperation of patients clinging to a last chance at life.
In Williamson's case, Genentech in South San Francisco has
denied him expanded access to anti-VEGF, an angiogenesis inhibitor
that might hinder the growth of cancer tumors by starving their
blood supply.
Dr. Sue Hellman, the chief medical officer and senior vice
president of Genentech, said the company only produces enough of
the drug for the patients in the clinical trials.
This is especially true for anti-VEGF. Because it is a
monoclonal antibody, a protein that must be produced by living
cells, it is extremely difficult -- and expensive -- to manufacture.
Only if enough evidence of safety and possible effectiveness
emerges at the end of phase 2 trials would the company consider
setting up an expanded access program, Hellman said. Supplying the
drug outside controlled trials without evidence that it might help
the patient would be premature, she argued, as well as
``potentially foolish'' and ``costly for the company.''
She pointed out that if Genentech provided a drug to a single
patient, company policy states that a program must be set in place
to provide the drug to multiple patients.
Dr. Howard Jaffe, senior vice president of drug development at
Gilead Sciences in Foster City, added that it's rarely only one
person who wants the drug. ``We get these calls every day,'' he
said.
Gilead has 9,000 patients enrolled in an expanded access program
for adefovir dipivoxil, an anti-HIV drug that is on an accelerated
approval process at the FDA.
Jaffe said he gets about 20 requests per week for adefovir
dipivoxil, which is also going through phase 3 clinical trials for
the treatment of chronic hepatitis B virus infection.
At some point, he said, the demand outpaces the company's
ability to meet it. ``Where do you draw the line?'' he said.
Researchers also worry that providing drugs outside the
carefully controlled clinical studies risks clouding up the
investigation, and might ultimately slow approval.
``If you do compassionate-use studies, they're still studies,''
said Dr. Larry Hirsch, a spokesman for Merck Research Laboratories
in New Jersey. ``We're still responsible for communicating any
experience with the drug to the FDA.''
Months earlier, Williamson was denied entrance into a controlled
clinical trial for anti-VEGF because investigators were concerned
his liver was not functioning properly.
Trial researchers have since reconsidered, but Williamson argues
that he is now in such an advanced stage of the disease that he
cannot bear the trip to Bethesda, Md., where the studies are being
conducted.
``Whenever we administer anything to a patient, and if anything
untoward happens, we're left trying to determine what was the cause
and effect,'' Hirsch said. ``We consume time and resources trying
to understand those incidents.''
Expanded access programs mix politics and public relations, said
Fran Visco, president of the National Breast Cancer Coalition in
Washington, D.C. Visco advised Genentech when the company was
developing its expanded access program for Herceptin.
``I don't think any biotech company puts an expanded access
program into place without pressure,'' she said.
But Jaffe said well-organized expanded access trials can do more
than polish a company's relations with the public. ``You're
learning more about a drug in as near a market setting as
possible,'' he said. ``It's like a big field test.''
In a financial sense, Jaffe added, the programs also help
develop a group of patients who might continue using the drug after
it is marketed.
Richard Klein, the HIV/AIDS program coordinator at the FDA's
Office of Special Health Issues in Maryland, said his biggest
concern about expanded access is that people go into experimental
trials with unrealistic expectations.
``People often assume if something is coming down the pipe, it's
better,'' he said. ``But it's still research, and that means it has
a lot of risks.''
These patients, saidcKlein, are often left ``grasping pieces of
wood from a sinking ship. But we have to put the wood there.''
As for Williamson, he understands the drug might do little or
nothing to stop his kidney cancer from advancing. But he said that
companies hoh potential influence over a person's life should still
be bound by a moral imperative, when asked, to help those with no
other choice.
``If a company is going to make millions of dollars selling a
product to the public,'' he said, ``shouldn't they be at least
slightly beholden to that public, before (the drug) is approved by
the FDA and while they have to pay for the drug?
``The reality of my situation is that this anti-VEGF, I probably
won't get it,'' he said. ``And even if I did get it, it probably
wouldn't save my life. The most I could hope for is a stabilization
of my disease.''
