NIH Funding of Gene Therapy Trials

Abstract

Several recent editorials in Molecular Therapy have commented on the funding of gene therapy clinical trials by the National Institutes of Health (NIH), and the difficulties arising due to the existence of numerous, often overlapping, regulatory reviews required by local and federal agencies. Under the leadership of Dr. Theodore Friedmann, the American Society of Gene Therapy (ASGT) has now taken the lead in identifying ways to improve the process of funding gene therapy vector production and clinical trials by the NIH As with regulatory review, the current method of trial funding is fragmented. Preclinical development is often funded via individual investigator grants, such as R01s and program grants. While these grants are the lifeblood of basic research in the US, they may be less well suited to support the broad scope of translational research. In fact, vector production and toxicology has often been reviewed via a mechanism involving the National Gene Vector Laboratories (NGVL). Funding of vector production that has been approved by the NGVL then falls upon individual NIH institutes, which may not decide to provide funding. Whereas the funding of clinical trials is not built into this mechanism, the review of vector production often requires clinical protocols to be submitted along with preclinical data and vector details. Furthermore, funding of the actual clinical trial is not guaranteed, even if the vector has been produced and certified for human use at significant cost. Neverthless, application for this funding must be pursued prior to or concurrently with regulatory (Institutional Review Board, Food and Drug Administration, NIH Recombinant DNA Advisory Committee) reviews. The predictable result is a complicated, disjointed process of vector and protocol development and approval that often leads to disparate demands on the investigator attempting to open a clinical trial. Clearly, the field needs a more unified and coordinated approach to funding. In addition to this disjointed approach to funding of vector production, toxicology and clinical trials, several NIH institutes have now developed alternative mechanisms for vector production, potentially adding yet another layer of review. At the least, implementation of this separate mechanism of vector production will require duplication of much of the expertise that has already been developed in the NGVL program. The NGVL, which was initially envisioned as a trans-NIH approach to the high costs of vector production, has met with notable successes—including, for instance, production of the vector utilized in the recently announced and highly publicized National Cancer Institute trial in melanoma. Following discussions with several NIH institutes, Dr. Friedmann appointed an ad hoc committee to examine these issues and to make recommendations on how to better leverage NIH funding for the purpose of supporting gene therapy trials. The committee, led by Dr. Arthur Nienhuis, has met several times in the past month and will forward recommendations to the ASGT Board for further discussion and input. This is clearly a step in the right direction. If ASGT does not advocate for more efficient and thoughtful support of human trials utilizing gene transfer technology, no one else with any political clout is likely to do so. Optimistically, NIH will value the input and utilize the ideas in tackling this issue. This process may provide a template for how the ASGT could help address the other major challenge clinical researchers face in this field: the multiple, and in some respects redundant, regulatory processes required to open a gene therapy trial. A long-term goal might then be a unified approach to funding linked to a more harmonized regulatory review process. While these changes will clearly be difficult to implement, if they were eventually accomplished, they would allow better long-term planning and allocation of institutional resources and greater efficiency in the use of NIH funding. Ultimately, this approach may be necessary to take advantage of the large amount of funding invested in basic vector research and the promising developments that have been seen in early trials in several diseases.