Dec. 1, 2017: Accelerating Gene Therapy

I have previously written of NCATS’ work to accelerate the development of various types of therapeutics. From small molecules to proteins to stem cells, each modality works in a different way to reverse a disease process. I want to bring you up to date on some of the work NCATS is doing using DNA or RNA genes to treat diseases, aka “gene therapy”. 

In August 2017, the Food and Drug Administration (FDA) approved its first U.S. gene therapy product: a treatment for cancer in which a therapeutic gene is delivered to a patient’s blood cells outside the body and the cells are then delivered to the patient. This process is sometimes termed “ex vivo” gene therapy. Two months later, in October, an expert advisory panel to the FDA unanimously endorsed a gene therapy delivered directly to the patient, (“in vivo” gene therapy), in this case, to the retina of the eye to treat a rare form of hereditary blindness.

These important milestones are the most recent signs of the renaissance of gene therapy, a modality for which the translational chasm between promising concept and realized patient benefit has been unusually wide. But now the translational science of gene therapy has progressed to the point of clinical successes. 

NCATS is at the forefront of addressing translational challenges that have hindered progress in this field. For example, in my October 2017 Director’s Message, I wrote about a collaborative project within our Clinical and Translational Science Awards (CTSA) Program to more rapidly translate complex gene and cell therapies to early phase pediatric clinical trials. And, through our Therapeutics for Rare and Neglected Diseases (TRND) program last year, NCATS initiated a suite of gene therapy collaborations to develop solutions for bottlenecks limiting efficient gene therapy translation.

One of these TRND projects is a gene therapy for the rare pediatric disease aromatic L-amino acid decarboxylase (AADC) deficiency. Our project partner, Agilis Biotherapeutics, Inc., achieved a regulatory milestone when the FDA gave them the green light to file an application for approval to market the gene therapy to patients. Just one year earlier, the therapy had seemed destined to fail: Despite promising results in clinical trials outside of the U.S., the market for this disease is small and the work needed to proceed was seemingly insurmountable. NCATS teamed with Agilis to convert promise into reality, jointly creating a manufacturing process for the therapy that complies with FDA regulations and obtaining pre-clinical data required by the FDA. In addition to getting this potentially lifesaving therapy to patients, this project established technological and regulatory models that will accelerate the development of other rare disease gene therapies.

NCATS is now exploring ways to streamline the development of gene therapies generally. These treatments rely on delivery of the gene to a specific cell type, usually by a modified virus called a “vector.” I like to think of the vector as a suitcase carrying the gene, and currently, the FDA must evaluate both the suitcase and the gene inside with every new product.

One idea we are pursuing is the development of standard vectors — like standard-sized suitcases we use for travel — that could be used for multiple diseases that affect the same cell type. In this scenario, the manufacturing processes, safety and location of vector delivery of the gene would be known, so the FDA would only have to review the relevant gene being carried, reducing time to approval and making the process more cost-effective. NCATS requested information on this approach from the scientific, regulatory, industry and patient communities this fall, and we now have received feedback that will help us identify opportunities, challenges and translational science needs for platform vector gene therapy.

These efforts that involve multiple NCATS programs, institutions and public-private partnerships exemplify our guiding principles that “translation is a team sport,” and that therefore, “if you want to go far, go together.” Together, we are going far in gene therapy.

Christopher P. Austin, M.D.
National Center for Advancing Translational Sciences