Successfully Navigating Food and Drug Administration Orphan Drug and Rare Pediatric Disease Designations for AAV9-hPCCA Gene Therapy: The National Institutes of Health Platform Vector Gene Therapy Experience.

Orphan drug designation (ODD) is an important program intended to facilitate the development of orphan drugs in the United States. An orphan drug benefiting pediatric patients can qualify as a drug for a Rare Pediatric Disease Designation (RPDD) as well. The ODD and RPDD programs provide financial incentives for development of diagnostic drugs, preventive measures, and treatment of diseases affecting small patient populations (adult and pediatric) for which commercial development would otherwise be very challenging. In 2019, a multidisciplinary group of collaborators at National Institutes of Health (NIH) embarked upon a gene therapy platform program called Platform Vector Gene Therapy (PaVe-GT) intended to develop gene therapies for four such rare disorders. An important part of PaVe-GT is to publicly share scientific and regulatory experience gained at different stages during the implementation of the PaVe-GT platform utilizing illustrative examples. The PaVe-GT team recently obtained ODD and RPDD for an adeno-associated virus gene therapy to treat propionic acidemia. Given an increasing interest in obtaining ODD for gene therapy, especially by small companies, research investigators, and patient groups, we overview the submission process and subsequently provide examples of our ODD and RPDD applications. Our ODD and RPDD applications and templates can also be found on the PaVe-GT website. Shared reference documents will have great utility to assist parties who may have limited experience with the preparation of similar applications for their orphan product.