FDA, NIH, and 15 private organizations join forces to increase effective gene therapies for rare diseases

The U.S. Food and Drug Administration, the National Institutes of Health, 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 heritable 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.

"By leveraging on experience with a platform technology and by standardizing processes, gene therapy product development can be accelerated to allow more timely access to promising new therapies for patients who need them most," said Peter Marks, M.D., Ph.D., Director of the Food and Drug Administration (FDA)'s Center for Biologics Evaluation and Research. "FDA is committed to developing a regulatory paradigm that can advance gene therapies to meet the needs of patients 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, M.D., Ph.D. "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.

"Rare diseases affect 25 to 30 million Americans, but because any given rare disorder affects so few patients, companies often are reluctant or unable to invest the years of research and millions of dollars necessary to develop, test and bring individualized gene therapy treatments for a single disease to market," said Joni L. Rutter, Ph.D., acting director of NIH's National Center for Advancing Translational Sciences (NCATS). "The BGTC aims to make it easier, faster and less expensive to pursue bespoke gene therapies in order to incentivize more companies to invest in this space and bring treatments to patients."

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.

Private partners include Biogen Inc., Cambridge, Massachusetts; Janssen Research & Development, LLC, Raritan, New Jersey; Novartis Institutes for BioMedical Research, Cambridge, Massachusetts; Pfizer Inc., New York, New York; REGENXBIO Inc., Rockville, Maryland.; Spark Therapeutics, Philadelphia, Pennsylvania; Takeda Pharmaceutical Company Limited, Deerfield, Illinois; Taysha Gene Therapies, Dallas, Texas; Thermo Fisher Scientific Inc., Waltham, Massachusetts; and Ultragenyx Pharmaceutical, Novato, California. Several non-profit partners also are involved, including the Alliance for Regenerative Medicine (ARM), Washington, D.C.; the American Society of Gene and Cell Therapy, Milwaukee, Wisconsin; CureDuchenne, Newport Beach, California; National Organization for Rare Disorders (NORD), Quincy, Massachusetts; and The National Institute for Innovation in Manufacturing Biopharmaceuticals (NIIMBL), Newark, Delaware.

In addition to NCATS, participating NIH institutes include the Eunice Kennedy Shriver National Institute of Child Health and Human Development; National Eye Institute; National Heart, Lung, and Blood Institute; National Human Genome Research Institute; National Institute of Arthritis and Musculoskeletal and Skin Diseases; National Institute of Dental and Craniofacial Research; National Institute of Mental Health; National Institute of Neurological Disorders and Stroke; and National Institute on Deafness and Other Communication Disorders.

The BGTC is the first AMP initiative focused on rare diseases. Other ongoing AMP projects bring together scientific talent and financial resources from academia, industry, philanthropy, and government, and focus on improving the productivity of therapeutic development for common metabolic diseases, schizophrenia, Parkinson’s disease, Alzheimer’s disease, type 2 diabetes and autoimmune disorders rheumatoid arthritis and systemic lupus erythematosus.

About the Foundation for the National Institutes of Health

The Foundation for the National Institutes of Health (FNIH) creates and manages alliances with public and private institutions in support of the mission of the NIH. The FNIH works with its partners to accelerate biomedical research and strategies against diseases and health concerns in the United States and across the globe. Established by Congress in 1990, the FNIH is a not-for-profit 501(c)(3) charitable organization.

About the National Center for Advancing Translational Sciences (NCATS)

NCATS conducts and supports research on the science and operation of translation - the process by which interventions to improve health are developed and implemented - to allow more treatments to get to more patients more quickly.

About the Food and Drug Administration (FDA)

The FDA, an agency within the U.S. Department of Health and Human Services, protects the public health by assuring the safety, effectiveness, and security of human and veterinary drugs, vaccines and other biological products for human use, and medical devices. The agency also is responsible for the safety and security of our nation’s food supply, cosmetics, dietary supplements, products that give off electronic radiation, and for regulating tobacco products.

About the National Institutes of Health (NIH)

NIH, the nation's medical research agency, includes 27 Institutes and Centers and is a component of the U.S. Department of Health and Human Services. NIH is the primary federal agency conducting and supporting basic, clinical, and translational medical research, and is investigating the causes, treatments, and cures for both common and rare diseases.