The U.S. Food and Drug Administration (FDA), the National Institutes of Health (NIH), 10 pharmaceutical companies and five non-profit organizations have partnered to accelerate development of gene therapies for the 30 million Americans who suffer from a rare disease.
While there are approximately 7,000 rare diseases, only two inheritable diseases currently have FDA-approved gene therapies. The newly launched Bespoke Gene Therapy Consortium (BGTC), part of the NIH Accelerating Medicines Partnership (AMP) program and project-managed by the Foundation for the National Institutes of Health (FNIH), aims to optimize and streamline the gene therapy development process to help fill the unmet medical needs of people with rare diseases.
“Most rare diseases are caused by a defect in a single gene that could potentially be targeted with a customized or ‘bespoke’ therapy that corrects or replaces the defective gene,” said NIH Director Francis S. Collins, MD, PhD. “There are now significant opportunities to improve the complex development process for gene therapies that would accelerate scientific progress and, most importantly, provide benefit to patients by increasing the number of effective gene therapies.”
A single rare disease affects small numbers of people, but rare diseases collectively affect millions. Most rare inherited diseases stem from a specific gene mutation that is already known, making gene therapy a promising therapeutic approach. However, gene therapy development for rare diseases is highly complex, time consuming and expensive. Moreover, the development process is stymied by limited access to tools and technologies, lack of standards across the field, and a one-disease-at-a-time approach to therapeutic development. A standardized therapeutic development model that includes a common gene delivery technology (a vector) could allow for a more efficient approach to specific gene therapies, saving time and cost.
A primary aim of BGTC is to improve understanding of the basic biology of a common gene delivery vector known as the adeno-associated virus (AAV). BGTC researchers will examine the biological and mechanistic steps involved in AAV vector production, vector delivery of genes into human cells and how therapeutic genes are activated in target cells. These results will provide important information for improving the efficiency of vector manufacturing and enhancing the overall therapeutic benefit of AAV gene therapy.
To improve and accelerate gene and vector manufacturing and production processes, the BGTC program will develop a standard set of analytic tests to apply to the manufacture of viral vectors made by consortium researchers. Such tests could be broadly applicable to different manufacturing methods and make the process of developing gene therapies for very rare conditions much more efficient.
A clinical component of BGTC-funded research will support between four and six clinical trials, each focused on a different rare disease. These diseases are expected to be rare, single-gene diseases with no gene therapies or commercial programs in development and that already have substantial groundwork in place to rapidly initiate preclinical and clinical studies. The trials will employ different types of AAV vectors that have been used before in clinical trials. For these trials, the BGTC will aim to shorten the path from studies in animal models of disease to human clinical trials.
The BGTC also will explore methods to streamline regulatory requirements and processes for the FDA approval of safe and effective gene therapies, including developing standardized approaches to preclinical testing (e.g., toxicology studies).
NIH and private partners will contribute approximately $76 million over five years to support BGTC-funded projects. This includes about $39.5 million from the participating NIH institutes and centers, pending availability of funds. NCATS, which developed the related Platform Vector Gene Therapy (PaVe-GT) program and is the NIH lead institute for BGTC, expects to contribute approximately $8 million over five years.