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8-Humans: F.D.A. suspends a third of all gene therapy trials

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                                  PART I
-------------------------------- GENET-news --------------------------------

TITLE:  F.D.A. Suspends a Third of All Gene Therapy Trials
SOURCE: Associated Press
DATE:   Jan 14, 2003

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F.D.A. Suspends a Third of All Gene Therapy Trials

WASHINGTON (AP) -- A second European toddler apparently suffered a leukemia-
like side effect from gene therapy that cured him of the rare but deadly 
"bubble boy disease," prompting the government on Tuesday to suspend 27 
more gene therapy studies while they investigate the risk.

Bubble boy disease -- an immune disorder formally called severe combined 
immunodeficiency, or SCID -- is the only disease ever to be cured with gene 

But three months ago, a boy whose life was saved by a SCID gene therapy 
experiment in France when he was a baby came down with a leukemia-like 
syndrome at age 3.

Scientists have long warned that cancer is a possible risk from any gene 
therapy, such as that for SCID, that uses retroviruses, a type of virus 
that permanently invades cells, to deliver new genes into a patient's body. 
Still, no one else given gene therapy for SCID or other diseases had ever 
had such a side effect.

That first ill toddler prompted U.S. and French scientists in October to 
stop gene therapy experiments for SCID, including three in this country.

Now a second toddler in the French SCID experiment has come down with that 
same leukemia-like side effect, Food and Drug Administration scientists 
announced Tuesday.

Quietly notified by French researchers about a month ago, the FDA decided 
that the second serious side effect warranted a bigger precaution: 
Temporarily stopping about 27 more U.S. experiments that use retroviruses 
to insert new genes into blood stem cells in hopes of fighting diseases 
other than SCID.

The FDA didn't release a list of the experiments but said they include some 
targeting such diseases as cancer and include several hundred participants.

The FDA said if researchers argue any of the retrovirus experiments offer a 
sole option to people with life-threatening illnesses, the agency will work 
to let them restart on a case-by-case basis, with appropriate warnings to 
participants. Gene therapy for SCID, however, appears to be on hold 

"We do think it's a prudent course," because "there are things going on 
here that we really don't understand," said FDA gene therapy chief Dr. Phil 

The FDA will convene its scientific advisers next month to pore over the 
research and debate future steps.

"It's very unfortunate that with the first real success in a very difficult 
disease, that there's this downside," said American Society for Gene 
Therapy president Joe Glorioso, a University of Pittsburgh geneticist.

Without the gene therapy, these two boys almost certainly would have died 
of their SCID because they had no other treatment options, he noted. Yet 
without the gene therapy, he said, "it's unlikely these patients would have 
ever developed leukemia."

Both boys responded well to chemotherapy and are stable, but their long-
term outlook is uncertain, Noguchi said. He released few details about the 
second patient, including his nationality, other than that he was cured of 
SCID as a baby and became ill with the cancer-like syndrome almost three 
years later.

SCID babies are born without the ability to produce disease-fighting immune 
cells. The best known victim was David, Houston's famous "bubble boy" who 
lived in a germ-proof enclosure until his death at age 12 in 1984.

There are some SCID treatments, including bone marrow transplants that can 
allow patients to live normal lives. But transplant success varies widely, 
and many children still die young.

So Paris' Dr. Alain Fischer generated great excitement when his gene 
therapy apparently cured nine of the 11 boys he treated who had the most 
severe SCID-type, called X-SCID. He drew bone marrow from the boys, culled 
immune cell-creating stem cells from it, and mixed in a virus containing 
the gene their bodies lacked. Injected back into their bodies, the stem 
cells worked properly.

                                  PART II
-------------------------------- GENET-news --------------------------------

SOURCE: U.S. Food and Drug Administration, FDA Talk Paper
DATE:   Jan 14, 2003

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FDA Talk Papers are prepared by the Press Office to guide FDA personnel in 
responding with consistency and accuracy to questions from the public on 
subjects of current interest. Talk Papers are subject to change as more 
information becomes available.

January 14, 2003
Media Inquiries: +1-301-827-6242
Consumer Inquiries: +1-888-INFO-FDA

Agency Action Provides Way for Patients to Continue Therapy Under Certain 
Circumstances if Additional Measures Taken

In a precautionary measure, the Food and Drug Administration (FDA) today 
placed on "clinical hold" all active gene therapy trials using retroviral 
vectors to insert genes into blood stem cells.

FDA took this action after it learned that a second child treated in a 
French gene therapy trial has developed a leukemia-like condition. Both 
this child, and another who had developed a similar condition last August, 
had been successfully treated by gene therapy for X-linked severe combined 
immunodeficiency disease (X-SCID), also known as "bubble baby syndrome."

Infants with X-SCID have a gene defect that leads to a complete lack of 
white blood cells that can fight infection. Without treatment, they die 
from complications of infectious diseases during the first year of life. 
The only treatment for this condition is a bone marrow transplant.

In early results of the French study in which a normal gene is inserted 
into blood stem cells of patients with X-SCID, nine of the 11 children had 
promising results and could leave the hospital and lead relatively normal 

After notification of the first case last year, FDA identified the three 
U.S. gene therapy studies that most closely resembled the French trial and 
stopped enrollment of human subjects in those trials. They remain on 
clinical hold, a condition which FDA can impose when adverse events or 
other safety questions arise during a clinical study.

FDA's continuing review of adverse event reports from all U.S. studies 
involving retroviral vectors has to date found no evidence of leukemia 
caused by the gene therapy. Moreover, the agency has to consider the 
potential risks of any experimental therapy within the context of the 
disease it may treat - in this case a devastating disease in children.

FDA's action includes a temporary hold on the enrollment of new patients in 
a subset of gene therapy trials that involve the use of retroviruses to 
insert new genes in blood stem cells, irrespective of the disease condition.

The temporary hold reflects FDA's appreciation that some of these trials 
involve patient populations and gene therapy products that may be 
appropriate to continue after they are updated to reflect this new risk 
information. FDA will consider and evaluate specific requests for clinical 
indications for fatal or life-threatening disorders for which there are no 
viable alternative treatments. In all cases, sponsors will need to inform 
treated and new subjects of the two adverse events, and will need to have a 
plan to actively monitor subjects for leukemia like events.

FDA continues to review the data from the adverse event in France, as well 
as the risks and potential benefits of all ongoing gene therapy trials, and 
will continue to work closely with the National Institute of Health's 
Office of Biotechnology Activities to oversee gene therapy studies in the 

The agency expects to hold an advisory committee meeting late next month to 
discuss the new adverse event in particular and retroviral gene therapy in 



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