FDA, NIH, and 15 Private Organizations Join Forces to Develop Gene Therapies for Rare Diseases

FDA, NIH, and 15 Private Organizations Join Forces to Develop Gene Therapies for Rare Diseases

January 11, 2022

The US Food and Drug Administration (FDA), the National Institutes of Health (NIH), ten pharmaceutical companies, and five non-profit groups have teamed up to accelerate the development of gene therapies for the 30 million people in the United States who suffer from rare eye diseases.

Despite the fact that there are about 7,000 rare diseases, only two heritable diseases have FDA-approved gene therapies.

The newly launched Bespoke Gene Therapy Consortium (BGTC), which is managed by the Foundation for the National Institutes of Health (FNIH) and is part of the NIH Accelerating Medicines Partnership (AMP) program, aims to optimize and streamline the gene therapy development process to help meet 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.

“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,” Mr. Collins added.

A single rare disease affects a small number of people, but rare diseases affect millions of people. The majority of rare genetic disorders are caused by a specific gene mutation, making gene therapy a promising therapeutic approach.

However, developing gene therapies for rare diseases is highly difficult, time-consuming, and expensive. Furthermore, limited access to tools and technology, a lack of standards across the profession, and a one-disease-at-a-time approach to treatment development hinder the development process.

A standardized therapeutic development paradigm incorporating a common gene delivery method (a vector) could allow a more efficient approach to specialized gene therapies, saving time and money.

BGTC's main goal is to better understand the basic biology of the adeno-associated virus (AAV), known as a common gene delivery vector.

The molecular and mechanistic steps involved in AAV vector production, vector delivery of genes into human cells, and how therapeutic genes are activated in target cells will be investigated by BGTC researchers.

These findings will help improve the efficiency of vector production while also increasing the overall therapeutic benefit of AAV gene therapy.

The BGTC initiative will produce a standard set of analytic tests to apply to the manufacture of viral vectors made by consortium researchers in order to improve and accelerate gene and vector manufacturing and production processes.

Such tests might be used to examine a variety of production methods, making the process of creating gene therapies for extremely rare diseases far 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 likely to be rare, single-gene disorders with no gene therapies or commercial programs in development, as well as diseases with extensive preclinical and clinical research already underway.

The trials will use a variety of AAV vectors that have already been employed in clinical trials. For these trials, the BGTC aims to decrease the time between investigations in animal models of disease and human clinical trials.

The BGTC will also look into ways to simplify regulatory criteria and processes for FDA approval of safe and effective gene therapies, such as adopting standardized preclinical testing approaches (e.g., toxicology studies).

NIH and private business partners will provide $76 million over five years to support BGTC-funded research. This includes about $39.5 million from the collaborating NIH institutes and centers, pending availability of funds.

NCATS, which is the NIH lead institute for BGTC and developed the related Platform Vector Gene Therapy (PaVe-GT) program, also expects to provide $8 million over five years.

Private partners include Biogen Inc.; Janssen Research & Development, Novartis Institutes for BioMedical Research, Pfizer Inc., REGENXBIO Inc., Spark Therapeutics, Takeda Pharmaceutical Company Limited, Taysha Gene Therapies, Thermo Fisher Scientific Inc., and Ultragenyx Pharmaceutical.

Several non-profit partners also are involved, including the Alliance for Regenerative Medicine (ARM), the American Society of Gene and Cell Therapy, CureDuchenne, National Organization for Rare Disorders (NORD), and The National Institute for Innovation in Manufacturing Biopharmaceuticals (NIIMBL).

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.