Guest guest Posted February 24, 2003 Report Share Posted February 24, 2003 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. Gettingwell- / Vitamins, Herbs, Aminos, etc. To , e-mail to: Gettingwell- Or, go to our group site: Gettingwell Tax Center - forms, calculators, tips, and more Quote Link to comment Share on other sites More sharing options...
Recommended Posts
Join the conversation
You are posting as a guest. If you have an account, sign in now to post with your account.
Note: Your post will require moderator approval before it will be visible.