The FDA is past its expiration date in a world of gene therapies.
http://reason.com/rb/rb010902.shtml
January 9, 2002
Being too cautious can kill you.
And the U.S. Food and Drug Administration (FDA) is the avatar of bureaucratic
caution.
Consider the FDA’s recent responses
to setbacks in gene therapy research. In September 1999, 18-year-old Jesse
Gelsinger died four days after receiving a novel gene therapy aimed at
correcting a genetic disease that prevented his liver from processing proteins
properly. His disease, ornithine transcarbamylase deficiency, occurs in
one in 40,000 births and usually kills babies born with it within a few
days after birth.
The physician scientists at the Institute
for Human Genetic Therapy (IHGT) at the University of Pennsylvania infused
attenuated cold viruses containing the normal gene directly into Gelsinger’s
liver. This phase one clinical trial was designed to check on the safety
of the treatment -- it was not expected to cure Gelsinger or other participants
in the study.
After the gene therapy was administered,
Gelsinger suffered an immediate strong immune reaction that led to his
death four days later. The Gelsinger family later claimed that they were
not given enough information for adequate informed consent. The IHGT researchers
argue that they had informed the family, but later settled out of court
for unspecified damages.
The FDA went into panic mode after
the Gelsinger story broke in The New York Times and The Washington Post.
The FDA began hastily scrutinizing all gene therapy trials with an eye
to finding not just egregious violations, but even technical paperwork
missteps. Spooked bureaucrats who want to stop something that they fear
might get them in trouble tend to bury those they regulate in mounds of
paper and interrogatories. .
Unfortunately, the research of Dr.
Jeffrey Isner fell victim to this FDA ass-covering effort. Dr. Isner and
his colleagues at St. Elizabeth’s Medical Center in Boston and at Tufts
University had begun very promising gene therapy research designed to repair
hearts damaged by atherosclerosis. Isner began clinical trials in 1998
in which the gene for vascular endothelial growth factor (VEGF) was inserted
directly into the blocked arteries of patients suffering from angina.
The idea is that the VEGF gene would
cause the patient’s heart to start growing new blood vessels to go around
the blocked ones, essentially growing their own heart bypasses without
surgery. The patients chosen for the research had tried all other treatments
for their heart disease, including heart bypasses and balloon angioplasty.
Most could barely walk 100 feet before experiencing crushing chest pain.
Despite some very positive preliminary
results the FDA shut down Isner’s gene therapy research because of technicalities
in March 2000, leaving many patients untreated. The FDA closed him down
because two patients in one of his clinical trials had died, but not from
side effects of the gene therapy. Since he had not reported those deaths,
the FDA bureaucrats couldn’t be sure that the treatment hadn’t killed them.
They followed the motto: When in doubt, shut it down. That some patients
died should not have been a surprise considering that only very desperately
ill people had been accepted into the trials in the first place. Isner
and his patients begged the FDA to reconsider, but the agency took its
time.
After being shut down, Isner and
his colleagues reported that in one trial 70 percent of the patients had
a significant decrease in angina symptoms. For example, one patient, the
Rev. Charles Wilson of Charlotte, N.C., told the Boston Herald that before
the gene therapy, he suffered "20 to 25 severe angina episodes a day. Something
as simple as shaving would bring on angina. Now, I’m back in the pulpit."
Rev. Wilson said that he was "baffled" by the FDA’s action against Isner.
A year and a half after the FDA stopped
the research, Isner published in the scientific journal Circulation the
results of one particular protocol in which all 13 patients treated with
VEGF were still alive, and nine had increased blood flow to damaged parts
of their hearts. In November, at the American Heart Association annual
convention, Isner’s colleagues reported a double-blind study of 19 patients
in which 12 patients received VEGF and seven did not. Eight of the 12 treated
with VEGF had increased blood flow to their hearts. In other words, gene
therapy worked.
Tragically, Isner didn’t get to savor
his triumph over the bureaucrats. He dropped dead of a heart attack on
October 31. And it is very likely that many patients who might have benefited
directly from participating in this clinical trial also dropped dead while
the FDA dithered. That’s not to mention the deaths that will result from
the delay in eventually rolling this treatment out to the more than 250,000
Americans who suffer from angina.
"Among bureaucrats, the costs of
errors are thought to exceed the gains from risky choices, so excessive
caution or prudence is the norm," public choice economists Randy Simmons
and William Mitchell explained in their article "Pathological Politics"
in Society.
A frequent critic of the FDA, Sam
Kazman from the Competitive Enterprise Institute (CEI) in Washington, D.C.,
puts it more pointedly. "From a bureaucrat’s point of view, it’s a lot
more important to worry about preventing a single highly publicized death
like Jesse Gelsinger’s than to worry about the unreported dozens or even
hundreds of nameless patients who die because the FDA is delaying approval
of a new life-saving therapy."
As bad as the current FDA regulatory
system is with regard to getting novel gene therapies to patients, worse
may be in store for the age of individualized medicine now dawning. Researchers
are hard at work developing treatments that will be tailored for individual
patients, not just drugs that can be sold to millions. For example, one
type of cancer vaccine can be created using cells taken from each individual
patient’s tumor. Those vaccines will work, if at all, only for that specific
patient.
Dr. Robert Oldham, CEO of Cancer
Therapeutics, Inc., says, "Individualized therapies don’t fit well into
the FDA’s mass drug development paradigm." He believes that conducting
the double-blind studies using hundreds of patients that the FDA now requires
for new drugs would be inappropriate for such individualized treatments.
Dr. Oldham has concluded, "The FDA
is a barrier to developing effective new treatments." And he is not alone.
In four polls conducted by the Polling Company for CEI, nearly two-thirds
of doctors agreed that the FDA was too slow in approving new therapies.
"If the government approves a drug
that will save lives tomorrow," asks Kazman, "how many people died yesterday
waiting for the government to act?"
As medical treatments become more
individualized, that question will become ever more pressing.
Ronald Bailey is Reason's science
correspondent and the editor of Earth Report
Copyright (c) McGraw-Hill, 2002
By Ronald Bailey