Gene Therapy Platform for Rare Diseases

National Center For Advancing Translational Sciences

Investigators

Linked publications & trials

Abstract

The TRND Program initiated a suite of collaborations with biotech and academic groups that were strategically selected to serve as inaugural pilot projects. The overall goal is to enable TRND to build a gene therapy translation toolbox. New technologies to scale up gene vector manufacturing and to deliver the transgene to the right tissue at the right time and dosage are among those being developed at TRND. These technologies, along with best practices to achieve regulatory approval of gene therapy, will help improve the speed of development and reduce costs for gene therapy in general. The pilot projects include preclinical development of therapies for Duchenne muscular dystrophy, Pompe disease, and aromatic L-amino acid decarboxylase (AADC) deficiency. Pompe disease: During the collaboration with TRND, the adeno-associated virus (AAV) gene therapy technology was licensed by Asklepios BioPharmaceutical, Inc. AskBio formed a spin-out company, Actus Therapeutics, to continue clinical development and commercialization. The key preclinical support provided by TRND enabled the lead collaborator (Dr. Dwight Koeberl) to successfully obtain funding for his planned phase I trial in Pompe disease patients . TRND is co-funding the clinical trial through a cooperative agreement with the National Institute of Arthritis and Musculoskeletal and Skin Diseases (NIAMS). AADC deficiency: The team completed an end-of-phase 2 meeting with the U.S. Food and Drug Administration (FDA), to discuss the clinical data obtained from trials of AGIL-AADC conducted in Taiwan, and whether Agilis Biotherapeutics could proceed to seeking U.S. market approval without requiring additional bridging trials in the U.S. The clinical package, plus key preclinical safety, biodistribution, and chemistry, manufacturing and controls data developed by TRND, led FDA to agree that Agilis could proceed to file a Biologics Licensing Application (BLA) for marketing approval in the U.S. AGIL-AADC has received Orphan Drug and Rare Pediatric Disease designations in the U.S., as well as Orphan Medicinal Product status in Europe. The Orphan Drug designation provides access to the expedited Priority Review pathway at FDA, hastening patient access to AGIL-AADC by shortening the review of the marketing application by as much as four months.