Session III - Current Understanding of the Product Quality Attributes that Impact Safety and Efficacy of AAV-based Gene Therapy Products

Adeno-associated viral (AAV) vector-based gene therapy medicinal products hold curative promise for many disease indications. Although these products have been safely administered to hundreds of patients, recent safety issues have highlighted the need to close gaps in knowledge of product attributes and their potential impacts on safety and efficacy. The characterization and understanding of AAV-based gene therapies are improving, yet there remains much to be understood about the product quality attributes that impact safety and efficacy.  For example, improved understanding of attributes that impact duration of transgene expression, as well as immunogenicity, and removal of impurities such as capsids lacking the desired therapeutic genetic material, is of importance going forward. In September, 2021, the US FDA held an advisory committee meeting to discuss safety issues observed for a range of AAV-based products.  While the AdCom focused on clinical considerations, the aspects of product quality that may result in safety issues were not discussed in depth. In this session, presentations will address potential impacts of AAV gene therapy product quality attributes on safety and efficacy, innovative strategies and approaches for enhancing and optimizing vector performance, and limiting patient exposure to impurities. This will be followed by a discussion about where the industry is today with respect to characterizing AAV-based gene therapies, and where it is headed.