Page 38 - Read Online

Page 12 of 14 Brooks et al. Rare Dis Orphan Drugs J 2024;3:15 https://dx.doi.org/10.20517/rdodj.2023.27

therapies, with a specific focus on diseases of no current commercial interest. The first deliverable of the
BGTC is the Bespoke Gene Therapy Consortium (BGTC) Regulatory Playbook Version 1.0. This initial
version of the playbook is a comprehensive document outlining the clinical development process of AAV
gene therapy. While this version is quite generic, subsequent versions will include learnings from the work
of the BGTC, including efforts to develop standardized minimal sets of critical quality attributes for human
AAV gene therapies, as well as minimal sets of animal toxicology studies. The common goal of both the
BGTC and PaVe-GT efforts is to increase the efficiency of getting AAV gene therapies into first-in-human
trials, while protecting patient safety.

In the gene editing space, the NIH Somatic Cell Genome Editing program, supported by funds from the
NIH Common Fund, is accelerating genome editing technologies into the clinic. The first phase of the
program focused on technology development, with an emphasis on better ways to deliver genome editing in
different cells and tissues. The program developed a publicly available resource, called the SCGE Toolkit, to
make the data generated available to the public.

Phase 2 of the SCGE program is more focused on moving genome editing into the clinic. Specific initiatives
include developing technologies and assays for safety and efficacy studies; supporting genome editing-based
therapeutic leads through the IND phase; supporting novel platform genome editing clinical trials for more
than one disease; and a translational coordination and dissemination center for SCGE phase 2 projects.

Another initiative of SCGE Phase 2 is a prize competition, called the TARGETTED challenge, to identify
better technologies to deliver genome editors. There are two target areas: programmable solutions for
targeting genome editors to specific cells and tissues, and non-viral technologies to deliver genome editors
across the blood-brain barrier. The winners of the first phase of the challenge were announced in December
of 2023 (National Institutes of Health Announces Phase 1 Winners of the $6M TARGETED Challenge|
Freelancer), along with the opening of Phase 2 National Institutes of Health Announces Launch of Phase 2
of the $6M TARGETED Challenge|Freelancer .

Policy implications of gene-targeted therapy platforms
The rapid expansion and development of gene-targeted therapy platforms such as gene therapy, gene
editing, and other modalities stands in contrast to the traditional “one disease at a time” approach to rare
disease drug development. The implementation of such platforms represents an opportunity to bring gene-
targeted therapies to large numbers of patients with monogenic disease. However, such implementation
comes with substantial policy and economic challenges impacting the broader biomedical science,
regulatory, and healthcare enterprise. In 2021, DRDRI organized a series of meetings to discuss the
practical, financial, ethical, and regulatory issues posed by the broad implementation of gene-targeted
therapy platforms. The results of that meeting series were published in a Special Issue of
American Journal of Medical Genetics . Individual publications included discussion of readiness for gene-
[18]
[19]
[20]
[22]
[21]
targeted therapies , ethical and social implications , newborn screening , and economic implications .
CONCLUDING COMMENTS
In this article, we have highlighted some of the major rare diseases research activities supported by DRDRI.
While we have focused on DRDRI activities, we would like to emphasize that support of rare diseases
research at NCATS and NIH is not limited to DRDRI. Many of the other Divisions within NCATS support
some rare diseases research efforts. Notably, the NCATS Therapeutic Development Branch supports the
Therapeutics for Rare and Neglected Diseases program, which provides access to contract services to
accelerate rare disease translational science. Across NIH more broadly, many other Institutes and Centers at