Adeno-Associated Virus Gene Therapy Development: Early Planning and Regulatory Considerations to Advance the Platform Vector Gene Therapy Program

作者：Richa Madan Lomash, Jean Dehdashti, Oleg A. Shchelochkov, Randy J. Chandler, Lina Li, Irini Manoli, Jennifer L. Sloan, Pramod Terse, Xin Xu, Dimah Saade, Rodica Stan, PaVe-GT team, Philip J. Brooks, Donald C. Lo, C. Bönnemann, Charles P. Venditti, Anne Pariser, Elizabeth A. Ottinger · 发表于：Human Gene Therapy · 年份：2025 · DOI：10.1089/hum.2024.230 · 被引用次数：6 · 研究领域：Virus-based gene therapy research、CRISPR and Genetic Engineering、Viral Infectious Diseases and Gene Expression in Insects

Gene therapy development presents multiple challenges, and early planning is vital in the successful implementation of such programs. The Platform Vector Gene Therapy (PaVe-GT) program is a National Institutes of Health (NIH) initiative developing adeno-associated virus (AAV) gene therapies for four low-prevalence rare diseases. Utilizing the platform-based approach, the program aims to incorporate efficiencies throughout the preclinical and clinical development processes followed by public dissemination of scientific and regulatory learnings. Early in development, the establishment of a Target Product Profile (TPP) by the research team is a critical step to guide product development and align preclinical studies to clinical objectives. Based on the specific needs of the investigational product as defined in the TPP, an overall regulatory strategy can then be outlined to meet the regulatory requirements for the first-in-human clinical trials. During the preclinical phase of development, sponsors may request meetings with the Food and Drug Administration (FDA) to gather feedback on the planned studies and regulatory strategy. To pave the way for PaVe-GT's first investigational AAV gene therapy lead candidate, AAV9-hPCCA, we sought early feedback from the FDA utilizing an INitial Targeted Engagement for Regulatory Advice on CBER/CDER ProducTs (INTERACT) meeting. Here, we elaborate on the value of establishing a TPP and the FDA INTERACT meeting by including our initial AAV9-hPCC...