Adeno-associated virus (AAV) vectors are a leading platform for gene delivery for treating various human diseases. Pre-existing immunogenicity to AAVs may inhibit the effectiveness of AAV-based gene therapies, through immune clearance and neutralization of cell transduction functions, and may also trigger inflammatory responses which lead to adverse effects. For these reasons, it may be necessary to screen patients for the presence of pre-existing immunogenicity to AAVs before any treatment can be administered, which often takes the form of standard bioanalytical immunogenicity assays such as an anti-AAV total antibody assay (TAb) or a functional cell-based assay for detecting neutralizing antibodies (NAb) to the AAV serotype. The use of these bioanalytical assays for means of inclusion/exclusion of patients from enrollment in clinical trials then implicates these assays as an IVD companion diagnostic that is contemporaneously developed with the therapeutic drug for marketing approval. Since the result from these assays is used to enroll patients and the assays have not already received marketing authorization for that specific intended use, the IVD use in that context would be investigational it becomes subject to requirements of the Investigational Device Exemption (IDE) regulation. As many gene therapy companies begin this journey to the IDE pathway, there are many questions on the process and how that relates to their specific therapeutic programs. In this presentation, we share the insights we have gained from our interactions with regulatory agencies, consultants, and sponsors who are pursuing the path to IDE and IVD companion diagnostics.
Learning Objectives:
Upon completion, participants will be able to understand general concepts related to IVD companion diagnostics in clinical trial settings during drug development.
Upon completion, participants will be able to evaluate the multiple strategies for obtaining Investigational Device Exemptions (IDEs) for assays detecting antibodies against viral capsids for use in clinical trial enrollment.
Upon completion, participants will be able to utilize the lessons learned from IDE submissions for AAV antibody assays and consider how these can be applied to various scenarios for IDE submissions to support their drug programs.
