FDA Stops Researcher's Human Gene Therapy Experiments

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Sat Mar 4 13:19:19 EST 2000

FDA Stops Researcher's Human Gene Therapy Experiments
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By Deborah Nelson and Rick Weiss
Washington Post Staff Writers
Thursday, March 2, 2000; Page A8 

    The Food and Drug Administration has halted four human gene therapy
experiments conducted by a leading researcher who was trying to grow new blood
vessels in patients with heart disease and other circulatory problems. 
    Neither the FDA nor the company sponsoring the experiments would provide a
detailed explanation of why the agency had stopped the experiments, which were
led by Jeffrey Isner of Tufts University School of Medicine and St. Elizabeth's
Medical Center in Boston.
   The move comes on the heels of disclosures that Isner failed to promptly
report the deaths of two volunteers to the National Institutes of Health as
required by federal rules. Isner has said the deaths were not related to the
treatment. But Vascular Genetics of Durham, N.C., a company founded by Isner to
commercialize the technology, recently acknowledged that one of those deaths
remains unexplained.
    The FDA's move against Isner's research marks the second time in two months
that the agency has put human gene experiments on hold. In January, the agency
suspended the University of Pennsylvania's high-profile gene therapy program
after a federal investigation into a teenage patient's death there uncovered
scientific and regulatory lapses.
    The field of gene therapy, in which researchers give patients new genes in
an effort to cure cancer or other disorders, has been roiled with controversy
since the September death of that youth, Jesse Gelsinger--the first death
directly attributed to gene therapy. In the weeks after Gelsinger's death, The
Washington Post revealed that Isner and another gene therapy researcher, Ronald
Crystal of Cornell University Medical Center in New York, had not reported
patient deaths in compliance with NIH rules.
    A subsequent inquiry from Congress revealed that other gene therapy
researchers had similarly failed to report hundreds of "adverse events,"
including many deaths, prompting both the FDA and the NIH to start developing
strategies for increasing compliance with federal research rules. Meanwhile,
some researchers have begun to wonder openly whether the fledgling field, which
has failed to produce a single cure in 10 years of efforts on thousands of
patients, can survive much more airing of its problems.
    The latest action involves two experiments in which scientists gave new
genes to patients with coronary artery disease in an effort to help them grow
fresh vessels to increase blood flow to their hearts, and two experiments for
patients with painful vessel problems in their limbs. Unlike the Penn study,
which used potentially toxic viruses to deliver new genes to patients, Isner's
studies infused raw, or "naked" DNA into patients' vessels. The approach has
been touted by some as being safer than those using viruses.
    John Cumming, president of Vascular Genetics, said researchers in three of
those four studies had recently enrolled and treated their final volunteers.
But he was told by the FDA last week that the company must stop enrolling or
treating patients in its large, ongoing heart study, which was taking place at
medical centers around the nation. That study was the one in which the
unexplained death occurred last May, less than 24 hours after the gene
    Cumming would not talk about the FDA's specific concerns except to say that
the agency had requested additional data relating to the fate of the gene in
patients' bodies. He said he did not think that the FDA's action reflected any
agency concerns that the treatment might have caused any of the patient deaths
(a third death, in one of the limb vessel studies, occurred and was promptly
reported last fall). Rather, he said, the move reflected generic concerns about
the study that the company was already addressing.
    "We're putting together a full presentation for the FDA," Cumming said.
"Our philosophy is to err on the side of thoroughness. We are very comfortable
with the data."
    Cumming said the company had hoped to use the heart study's results to gain
FDA approval for a larger and final "pivotal" study, which could lead to
eventual marketing approval of the treatment. With only about three-quarters of
the intended volunteers enrolled to date, he said, and no clues about whether
or when the FDA might eventually allow the study to continue, it was not clear
whether the company would succeed in getting that study approved this year.
    FDA officials said it is the agency's policy not to comment when it puts an
experiment on "clinical hold," the technical term for the open-ended suspension
order imposed on the Isner experiments.
    Inder Verma, a gene therapy researcher at the Salk Institute in La Jolla,
Calif., and president of the American Society for Gene Therapy, said yesterday
he had not heard about the FDA's action against the Isner study but that the
field of gene therapy badly needed to regain a level of public trust. "If
people have not done the right thing," he said, "then they need to be held
    Vascular Genetics is being heavily underwritten by Human Genome Sciences
Inc., a Rockville biotechnology company that owns patent rights on the gene,
called VEGF-2, being studied in all four closed experiments. William Haseltine,
chairman and chief executive of Human Genome, said he did not foresee major
problems from the delay.
"Basically it's routine," he said. "It's a request for more and better
pharmacology to measure blood levels of VEGF-2. We think there's going to be no
trouble complying."
Staff writer Justin Gillis contributed to this report.
© 2000 The Washington Post Company 

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