ASGCT Grapples With Development for Ultra-Rare Diseases

Ultra-rare diseases challenge the typical commercial development model for gene therapies, resulting in significant questions for the field on how these barriers affect equitable access to the potential promise of these therapies. To begin to confront these issues, ASGCT convened stakeholders as part of a virtual event last week to discuss various approaches. Below are some highlights from speakers from governmental bodies, nonprofit organizations, and biotechnology companies on a variety of current, imminent, and potential solutions.

To address the lack of scalability of the development of one therapy at a time under proprietary conditions, government can play a role in providing the necessary infrastructure, according to Anne Pariser, M.D., director of the NCATS Office of Rare Disease Research. She explained that the Platform Vector Gene Therapy (PaVe GT) pilot project aims to increase the efficiency of clinical trial initiation by using a platform design—use of the same gene delivery system and production and purification methods—for gene therapies for four rare disease, with open access to data.

Using, and expanding upon, the principles of the PaVe GT project, the Bespoke Gene Therapy Consortium (BGTC), will provide additional supportive elements, including small batch manufacture of vector, standardization of clinical protocols, and a framework to manage IND and legal liabilities. This program is a public-private partnership led by the Foundation for the NIH, which will fund the development into clinical trials of gene therapies for five to six diseases that each affect less than about 100 people. The BGTC is an interim solution, according to FDA CBER director Peter Marks, M.D., Ph.D., to put together the pieces needed for efficient early development. Steven Hoffmann, associate vice president of research partnerships at the FNIH, said this project will come up with a model and regulatory framework for another entity to use to advance development of gene therapies for ultrarare diseases.

Nonprofit organizations, such as the Columbus Children’s Foundation, have developed a business model for the development of gene therapies for rare diseases. The Columbus Children’s Foundation aims to accelerate the development of gene therapies for ten rare diseases through a collaborative funding model—a nonprofit biotech with public and private support. Laura Hameed, the foundation’s executive director, emphasized the criticality of having industry partners to provide not only funding support, but also strong and deep expertise on clinical development and regulatory issues.

Similarly, Gaurav Shah, M.D., CEO of Rocket Pharmaceuticals, noted that partnership of patient organizations with the private sector can sometimes allow more rapid development due to access to capital. Biotechnology companies are able to develop gene therapies for ultra-rare diseases by including them in a portfolio that includes therapeutic development for other, less rare, conditions.

These nonprofit and private sector programs are individually developing a few gene therapies for ultra-rare diseases. Additionally, Marks stated that a sustainable ecosystem is needed—finding a model that provides some modest profit in an egalitarian way that is sustainable. Pariser suggested assembling 100 rare disease groups into a meta-group which, combined with sizable in-kind gifts, could be a larger-scale solution. ASGCT will continue to explore, educate, and advocate for these key issues surrounding equitable and efficient development of gene therapies for all who may benefit from them.