NCATS Receives FDA Rare Pediatric Disease Designation to Treat Propionic Acidemia

The U.S. Food and Drug Administration (FDA) has granted the National Institutes of Health’s National Center for Advancing Translational Sciences (NCATS) a Rare Pediatric Disease (RPD) designation for AAV9-hPCCA (NCATS-BL0746), an investigational gene therapy for the treatment of propionic acidemia (PA) resulting from the deficiency of propionyl-CoA carboxylase (PCC) due to mutations in its alpha subunit (PCCA).

The RPD designation is an important milestone in the process of securing a Priority Review Voucher (PRV), an incentive to expedite drug development. To qualify for the RPD designation, applicants must provide FDA data that suggests that an experimental drug may be effective in a rare disease that primarily affects a pediatric population. The FDA finalizes the RPD designation and RPD product designation on the basis of the information available at the time of marketing application, and awards a PRV to the sponsor of a qualifying approved application. PRV holders can use the PRV to expedite the FDA review process for a future marketing application or sell the voucher to a different sponsor. This is an incentive for orphan drug development for rare pediatric diseases because either option can result in a significant financial windfall.

Patients with PCCA-related PA cannot break down dietary protein, which leads to chronic, sometimes life-threatening conditions, including metabolic imbalance, cardiomyopathy, kidney disease, and other serious complications. Charles Venditti, M.D., Ph.D., Chief of the Metabolic Medicine Branch of the National Human Genome Research Institute, has studied PA and its potential treatments for many years. “The RPD designation speaks to the promise of AAV9-hPCCA for patients living with PCCA-related PA. If our planned clinical trial for AAV9-hPCCA is successful, an RPD designation could make it much more likely that all patients will be able to access this gene therapy.”

AAV9-hPCCA is one of four adenovirus-associated virus (AAV) gene therapies that will be developed in NCATS’ Platform Vector Gene Therapy (PaVe-GT) pilot project. PaVe-GT aims to increase the efficiency of clinical trial startup for gene therapies. AAV is a viral vector that has been used in multiple gene therapy clinical trials and is potentially useful for a significant percentage of genetic diseases.

“A major goal of PaVe-GT is to demystify the regulatory process for AAV gene therapies,” explains Elizabeth Ottinger, Ph.D., Acting Director and Head of Project Management of the NCATS Therapeutic Development Branch. “The PaVe-GT team has distilled and organized our insights on how to compile two important and highly interrelated designation applications: the RPD designation, and the Orphan Drug Designation (ODD). In coming weeks, we anticipate publishing a white paper with broadly useful advice about how we developed our applications for these designations.” Earlier this year, NCATS announced that FDA granted an ODD for AAV9-hPCCA.

“A unique element of PaVe-GT is our commitment to make our program results and regulatory documents publicly available,” notes P.J. Brooks, Ph.D., Acting Director of the NCATS’ Division of Rare Diseases Research Innovation. “In conjunction with the release of the upcoming white paper, we also anticipate releasing the designation requests that were submitted to the FDA. We believe that these materials will be useful to any party interested in developing gene therapies and will be especially useful for groups interested in developing gene therapies for diseases with very small populations.”

3/30/23 Update: Visit the PaVe-GT Resources page for RPD Designation resources, including the lightly redacted designation request for AAV9-hPCCA, and an RPD Designation request template.