US SUSPENDS GENE THERAPY TRIALS

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http://www.twnside.org.sg/title/service43.htm

 

THIRD WORLD NETWORK BIOSAFETY INFORMATION SERVICE

 

17 February 2003

 

Dear Friends and colleagues,

 

RE: US SUSPENDS GENE THERAPY TRIALS

 

Following the discovery that a second child treated in a French gene therapy

trial for severe combined immunodeficiency disease (SCID) has developed a

leukemia-like condition, the US Food and Drug Administration (FDA), in a

precautionary measure, placed on “clinical hold” all active gene therapy trials

similar to those of the French.

 

FDA’s action comes on the back of a temporary hold on the enrollment of new

patients into gene therapy trials that came into effect last year when a 3-year

old French boy, undergoing the gene therapy trials under Dr Alain Fischer of the

Necker Hospital in Paris, succumbed to cancer. This also prompted other European

authorities to halt similar new gene therapy trials in their own countries until

the problem was better understood.

 

However, now that a second child (whose details are not disclosed) had come

under the same leukemia-like side effect, the FDA has decided to take greater

precaution by temporarily stopping about 27 US experiments that use retroviral

vectors to insert genes into blood stem cells, similar to those in France, to

cures illnesses such as SCID.

 

Both the children are reported to be responding to chemotherapy and in stable

condition but their long-term conditions remain uncertain.

 

But FDA said it would consider allowing trials to proceed if retrovirus

experiments happen to be the only option to people with life-threatening

illnesses and this would be on a case-by-case basis with appropriate warnings

given to the subjects.

 

According to FDA gene therapy chief Dr Phil Noguchi, the action is prudent as

“there are things going on here that we really don’t understand.”

 

This is the third case in four years which exhibit the risk of gene therapy that

scientists had long warned about. In September 1999, an American teenager died

in a gene therapy experiment which was later criticized by the FDA for having

violated multiple safety rules.

 

As pointed out in the scientific article below, the hazards of gene therapy are

many. Although regulations have tightened, the technical and scientific problems

remain unsolved. Diseases are not understood, animal models are misleading,

vectors for delivering genes are ineffective and unsafe and the effects of genes

delivered cannot be predicted.

 

As such, a comprehensive review of gene therapy is urgently needed.

 

Below are three reports for your information:

 

1. FDA Places Temporary Halt on Gene Therapy Trials Using Retroviral Vectors

in Blood Stem Cells, US FDA, FDA Talk Paper, Jan 14, 2003

 

2. Second Boy Receiving Gene Therapy Develops Cancer, By Rick Weiss, The

Washington Post, Jan 15, 2003.

 

3. Genetically Modified Humans: For What and for Whom? By Dr. Mae-Wan Ho and

Prof. Joe Cummins, ISIS Feature

 

With best wishes,

 

Lim Li Lin and Chee Yoke Heong

Third World Network

121-S Jalan Utama

10450 Penang

Malaysia

 

Email: twnet

 

-----------------

 

REF: Doc.TWN/Biosafety/2003/J

 

Item 1

 

FDA Places Temporary Halt On Gene Therapy Trials Using Retroviral Vectors In

Blood Stem Cells

 

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

 

http://www.fda.gov/bbs/topics/ANSWERS/2003/ANS01190.html

 

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

 

FDA PLACES TEMPORARY HALT ON GENE THERAPY TRIALS USING RETROVIRAL VECTORS IN

BLOOD STEM CELLS

 

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 lives.

 

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 U.S.

 

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

general.

 

Item 2

 

Second Boy Receiving Gene Therapy Develops Cancer FDA Responds to Event in

France by Suspending 27 U.S. Studies Involving Similar Techniques

 

By Rick Weiss, The Washington Post, USA, Jan 15, 2003

 

http://www.washingtonpost.com/ac2/wp-dyn/A56894-2003Jan14?language

 

For the second time in four months, a child treated with an experimental gene

therapy in France has developed a form of leukemia apparently caused by the

treatment.

 

The new cancer case, in a boy who was given new genes to cure a severe immune

system deficiency, undercuts scientists’ initial hopes that the first case was a

fluke, and calls into question the value of the radical treatment, which had

been promoted as the first successful use of DNA to cure a disease.

 

In response, the Food and Drug Administration yesterday suspended as “a

precautionary measure” more than two dozen U.S. gene therapy studies that

involve techniques similar to those in the French experiment. Three U.S. gene

therapy studies that even more closely resemble the French experiment had

already been on hold since the first leukemia case came to light in September.

 

The new cancer case is a serious blow for an experimental field that has

struggled for a dozen years to produce its first cure and which suffered a

terrible setback in 1999 with the death of an American patient, Arizona teenager

Jesse Gelsinger. The approach involves the delivery of new genes to take over

for missing or broken ones.

 

Gelsinger died in a gene therapy experiment at the University of Pennsylvania

that was later heavily criticized by the FDA for violating basic safety rules.

But until the recent leukemia cases, gene therapy had at least seemed safe when

used in accordance with approved protocols. Now, scientists said, that sense of

safety has been undermined.

 

“When the first leukemia showed up, we as a community were certainly upset and

concerned about the patient,” said Joe Glorioso, president of the American

Society of Gene Therapy and chairman of molecular genetics and biochemistry at

the University of Pittsburgh Medical Center. “But when the second event

happened, that really is a red flag.”

 

Nonetheless, Glorioso and others noted, no cases of leukemia have been

documented in any of the thousands of other people who have received some form

of gene therapy, which suggests that the risk may be specific to this particular

disease or treatment plan. Researchers said they held out hope that they will

learn how to modify the treatment so it can still be used in children born with

the boys’ life-threatening disorder—severe combined immunodeficiency, or SCID.

Affected children can die from even minor infections, and the only cure—a bone

marrow transplant from a well-matched donor—is unavailable for many.

 

“We continue to see gene therapy as a promising therapy for all those who have

not benefited from current technologies,” said Philip Noguchi, acting director

of the FDA’s office of cellular, tissue and gene therapies, which regulates gene

therapy experiments in this country.

 

Noguchi praised the leader of the French study, Alain Fischer of the Necker

Hospital in Paris, for promptly informing the FDA about the new leukemia case

last month. The setback became public yesterday when the FDA placed a “clinical

hold” on all U.S. gene therapy experiments that, like the French experiment, use

retroviruses to deliver new genes into blood stem cells. The FDA hold demands

that studies already underway be stopped and enrollment of new patients be

suspended.

 

Noguchi estimated that 27 such trials have been approved in this country and are

at various stages of patient enrollment or testing. The agency will assess the

latest data at a Feb. 28 meeting, he said, but it may lift the hold on some

studies before then if it believes patients are more likely to be harmed by the

shutdown of a study.

 

Few details about the new case were available yesterday. The boy was one of

about 11 children treated by Fischer in the past several years, nine of whom

Fischer has said appear to be cured of their immune system disease. The

treatment uses retroviruses to deliver a crucial immune system gene to blood

cells.

 

Glorioso said yesterday he had been told that the latest leukemia case involved

a boy who was admitted to a hospital in Louisiana, suggesting he may be an

American who was treated in Paris.

 

In both leukemia cases, tests showed that the cancer was apparently triggered

when the newly delivered gene disrupted a nearby gene whose job is to help

prevent cancer.

 

Both boys have been treated for their leukemia and are “stable,” Noguchi said.

 

Staff researcher Lucy Shackelford contributed to this report.

 

 

 

Genetically Modified Humans: For What and for Whom?

 

By Dr. Mae-Wan Ho and Prof. Joe Cummins, ISIS Feature

 

A longer, referenced version of this article is available on ISIS members’

website (http://www.i-sis.org.uk)

 

Promises and perils

 

Gene therapy involves introducing genes into human cells in order to cure

diseases. Billions have been invested, and hundreds of clinical trials carried

out since 1990, mostly in the United States, but there has not been a single

documented case of the miracle cure that was promised.

 

It took the death of a healthy teenager Gelsinger in an early phase clinical

trial in September 1999 to alert the public to the hazards of gene therapy. The

US Food and Drug Administration (FDA) and the National Institutes of Health

(NIH) responded to widespread concern. Clinical trials were suspended. A public

enquiry turned up 652 cases of serious adverse events that went unreported,

along with seven other deaths. David Baltimore, Nobel laureate and president of

the biotech company Caltech with interests in gene therapy, declared, “ I

disagree we’ve had any benefit from gene therapy trials so far, many of us are

now asking, what the hell are we doing putting these things into people?”

 

To continue much more is on the site, click link at top of page.

 

Administrative changes were put in place amid calls for more research, and

clinical trials resumed with further promises. Although more stringent

regulation can tighten up the protocols and ensure quality control, the inherent

technical and scientific problems remain unsolved. Some of the necessary

research that should have been done long ago is only now being carried out,

revealing findings that confirm our worst fears.

 

 

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