ASGT Press Release 

Testimony in Senator Frist's Subcommittee Hearing on Gene Therapy

I am Savio L. C. Woo, Professor and Director at the Institute for Gene Therapy and Molecular Medicine at the Mount Sinai School of Medicine in New York, and I am currently serving as president of the American Society of Gene Therapy (ASGT). I am happy to testify on behalf of the Society, which is a non-profit, voluntary and professional organization. It was founded in 1996 with about 1000 members, and has grown to over 2000 members at present. The Society's mission is to promote research and education in all areas of gene therapy.

On March 7, 2000, the FDA and the NIH jointly announced two new initiatives to protect participants in gene therapy trials. The ASGT strongly supports the establishment of a regulatory system that will maximally ensure patient safety and provide investigative opportunities to produce useful outcomes in human gene transfer studies.

The first initiative, "Gene Therapy Clinical Trial Monitoring Plan", calls for sponsors of all gene therapy trials to establish monitoring plans that will need to be reviewed and approved by the FDA. To ensure the quality of monitoring, a key element in the plan is that it must be performed by a third party that is not directly involved with the study, such as independent clinical research organizations, which reports back to the sponsor. This procedure will be effective in trials where the sponsors and the investigators are separate entities, which constitute most of the industry-sponsored trials. However in trials where the sponsors and the investigators are the same individuals, which constitute most of the physician-sponsored trials in academia, the document recognized that the above procedure will result in the monitors reporting back to the investigators and the NIH will need to develop an appropriate procedure to assure independent monitoring. The challenge here will be to identify means in a scientifically and clinically sound way to ensure patient safety, but without incurring excessive costs that will stifle academic clinical research which are often more innovative, experimental in nature and pilot in scale. Furthermore, academic research also targets diseases that do not constitute large or lucrative markets to attract industrial investments and if these studies are not encouraged, many potentially treatable disorders will continue to exact a heavy toll in society. The ASGT will enthusiastically cooperate with the NIH and the FDA in developing such an effective and equitable monitoring procedure.

The initiative also calls for more rigorous quality control and assurance testing of gene therapy products. While appropriate for products used in more advanced clinical trials involving many patients, consideration will need to be given to the small-scale studies conducted by academic institutions in patients with life threatening conditions. The FDA recognized this limitation in the manufacture of monoclonal antibodies and introduced a distinct set of regulations for experimental studies of life threatening conditions. This foresight stimulated the successful application of monoclonal antibodies in an ever-broadening range of diseases to date, including breast cancer and lymphoma. A similar arrangement for gene therapeutics will stimulate clinical translational research and expedite development of novel treatments for life threatening diseases.

The second initiative," the Gene Transfer Safety Symposia", calls for the NIH and the FDA to offer 4 symposia annually to better educate clinical investigators and their team members on all aspects of clinical gene transfer studies, including and not limited to, good clinical practice in research, adverse events reporting and gene transfer product quality control and assurance. These symposia, such as the one scheduled for this afternoon, will be given by experts in the relevant fields and offered to all interested individuals and organizations in the country through tele-conferencing. The ASGT unequivocally supports this initiative, as a better educated clinical investigator will be better able to design and conduct clinical studies, as well as generate better quality results while better protecting patient safety at the same time. The initiative also calls for the FDA and the NIH to provide support for professional organizations and academic centers interested in holding safety conferences focused on gene therapy. The ASGT enthusiastically embraces this initiative and is in the process of organizing an intensive clinical gene transfer training course, together with the FDA and the NIH that will be offered over a 2-3 day period in conjunction with our Society's Annual Meetings in the future. Appropriate CME credits will be given, and certificates will be issued, to members who have successfully completed the training course.

Another area of major concern to the scientific community and the public is the real and/or perceived financial conflict of interest among investigators conducting clinical trials involving gene transfer. An extreme case would be that of an investigator conducting a clinical trial sponsored by a for-profit company that is partly or wholly owned by the same investigator. In order to ensure the safety and the interests of patients who voluntarily participate in clinical trials involving gene transfer, and to assure the public that these clinical studies are conducted without financial conflicts, ASGT members were notified of a newly adopted Society policy which states:

"In gene therapy trials, as in all other clinical trials, the best interest of the patients must be always primary. International, national and institutional guidelines on standards of care must be rigorously followed, approved protocols strictly adhered to, serious adverse events promptly reported to all appropriate regulatory and review bodies. Relevant federally and institutionally established regulations in financial conflicts must also be abided by. In addition, all investigators and team members directly responsible for patient selection, the informed consent process and/or clinical management in a trial must not have equity, stock options or comparable arrangements in companies sponsoring the trial. The American Society of Gene Therapy requests its members to abstain from or to discontinue any arrangement that is not consonant with this policy".

Gene therapy is a novel technology that promises to provide effective treatments for a variety of diseases in the future, and glimpses of hope that these promises will be fulfilled are coming to light. In a Phase I gene transfer trial of Hemophilia B at the Children Hospital of Philadelphia and Stanford University, significant reduction in whole blood clotting times was observed in patients receiving the lowest dose of a transfer vehicle containing the correct human gene. In another Phase I trial of Severe Combined Immune Deficiency Syndrome, better know as SCID or the bubble boy disease, several affected children treated with the normal human gene in France have reconstituted their immune systems for up to one year, and are now living normally with their families. While most encouraging, these results are still preliminary and further clinical studies must be conducted in order to ascertain that gene therapy is effective in curing these diseases.

What about other inherited disorders, or more complicated diseases like cancer, diabetes, heart disease, dementia, etc.? What are their prospects of being treated effectively by gene therapy as well? The reality is that gene therapy is a new biomedical discipline that is still in its infancy. In order to realize its full potential to treat a variety of diseases in the future, much basic science research and pre-clinical studies will need to be pursued to rigorously establish efficacy and safety in relevant animal models of disease. As biologic responses in cultured cells and in animals may or may not reflect what will actually happen in humans however, there can be no substitute to clinical testing of the new treatment modalities in patients. To assure the public that clinical gene transfer studies will be conducted by the investigators in a responsible manner, the American Society of Gene Therapy supports the refinement of federal regulatory processes that will simultaneously encourage research and ensure patient safety. This completes my testimony and I will be happy to answer any questions.