The National Institutes of Health (NIH) held its in-person Rare Disease Day at NIH convergence on February 28, 2023. This was the first time in a while that the event had been held in-person because of the COVID-19 pandemic. This event is meant to foster awareness about rare disease and also highlight the efforts of the NIH and its projects that are focused on improving outcomes in rare disease. One example is the Platform Vector Gene Therapy (PaVe-GT) initiative. During the event, there was a poster on display featuring this project. In order to learn more, Patient Worthy spoke with Rodica Stan, PhD, Senior Scientific Project Manager, Therapeutic Development Branch, Division of Preclinical Innovation, NCATS, to learn more.
What was the overarching goal of this project, and how was it achieved?
“The overarching goal of the PaVe-GT platform, which is one of our research projects at the National Center for Advancing Translational Sciences (NCATS), is to make gene therapy development and its clinical testing more efficient for rare diseases. The concept of this platform-vector approach is that of using the same gene delivery system and manufacturing methods for multiple rare disease gene therapies.
This process then reduces the inefficiencies a sponsor would normally encounter with developing and testing separate delivery systems, manufacturing methods, and other regulatory and clinical operations. PaVe-GT focuses on the adeno-associated virus (AAV) platform to develop gene therapies for four rare diseases.
As we continue to develop these therapies, we will make our data, documentation, and experience publicly available to help other rare disease groups developing gene therapies. We are currently somewhere in the middle of this research undertaking. In my poster, I showcased the regulatory road we have taken with the first gene therapy product for a rare disease called propionic acidemia (PA). This is important, as it will impact the regulatory strategy we plan to follow with the other three gene therapies of the platform.”
What were the results/conclusions of the study to develop a gene therapy development platform?
“Rare diseases are challenging in several ways. These include the diminished understanding of the natural history of the disease, difficulty in designing clinical trials due to small numbers of patients, and lack of commercial interest in developing new treatments for small populations. With PaVe-GT, we try to address as many of these challenges as possible.
The first platform product is AAV9-hPCCA, a gene therapy to treat PA resulting from a deficiency of propionyl CoA carboxylase alpha subunit (PCCA). In the development of this product, we benefited from the fact that the FDA, in their own endeavor to stimulate drug development, facilitate regulatory reviews (Initial Targeted Engagement for Regulatory Advice on CBER ProducTs, aka, INTERACT, & pre-IND meetings) and provide incentives (Orphan Drug Designation & Rare Pediatric Disease Designation) to drug developers.
For AAV9-hPCCA, we have met with the FDA as part of an INTERACT meeting, are currently planning the pre-IND meeting, and have already received the ODD and RPDD. In this context, we plan to leverage the experience and lessons learnt thus far with PaVe-GT program’s first product to contribute to reducing process redundancies and increasing efficiencies in the preclinical, regulatory, and clinical pathways for the other three PaVe-GT products under development. We are mid-way into this platform and have learnt some good lessons that will make the process more efficient, not only from a regulatory perspective, but also manufacturing and clinical, for the next products.”
What are the most important takeaways from the poster for the rare disease patient community? How will they be impacted?
“The most important takeaways from our research and the poster, which can resonate with the rare disease patient community, are that NCATS is vested in developing therapeutics for rare diseases and moreover, NCATS puts all effort into accelerating and streamlining this therapeutic development process. We believe in innovative therapeutic solutions, such as gene therapy, and we want to shorten the process taking therapeutic candidates from basic laboratory research to clinical testing. NCATS’ goal is to find more treatments for all people more quickly.”
What are some projects/areas of study in rare disease that you are looking forward to in the future?
“We are vested in programs such as PaVe-GT and many others. For example, we have worked on numerous projects that are part of the Therapeutics for Rare and Neglected Diseases (TRND) program. TRND supports research that overcomes the challenges with rare diseases I referred to earlier. Its mission is to accelerate the development of new treatments for diseases with high unmet medical needs.
Our Branch has contributed to TRND projects from lead optimization to clinical testing for rare diseases such as hemoglobinopathies, Jansen’s metaphyseal chondrodysplasia, Hermasnky-Pudlak syndrome, pulmonary fibrosis, Pompe disease, and many others. For these collaborations we work with other NIH and academic scientists, nonprofit organizations, and pharmaceutical and biotechnology companies. I am looking forward to NCATS expanding on this kind of projects focused on accelerating the therapeutic development path for many rare and neglected diseases.”
