Development of a risk register for Adeno-Associated Virus (AAV) based gene therapies

Authors

• L Bar
• RM Lomash
• N Terry
• J Todd
• R Stan

Abstract

Adeno-associated viruses (AAV) have proven to be an excellent tool for developing gene therapies, with a handful of FDA-approved AAV-based products to treat monogenic diseases through Q3 2024. Given the rapid growth of AAV-based treatments in development and the prevalence of rare monogenic disorders, it is valuable to document risks associated with the manufacturing and clinical administration of such therapies.  

The goal of this project is to create a risk register for AAV-based gene therapies to inform the development of future gene therapies, including those in the NIH Platform Vector Gene Therapy (PaVe-GT) program. PaVe-GT is a platform of AAV-based gene therapies targeting four rare diseases. To catalog negative risks (threats and limitations) and positive risks (opportunities) associated with the use of AAV-based gene therapies, we reviewed and analyzed peer-reviewed publications (PubMed), published conference abstracts (Embase), package inserts, and press releases. Of 248 sources identified in PubMed, the use of AAV gene therapies was described in clinical trials targeting over 35 diseases. Risks are categorized by AAV serotype, route of administration, and disease. Data are further disaggregated by risk descriptor, attribution, risk type, clinical trial phase, NCT Number, and source type. Common risks identified were associated with the AAV drug product, mode of administration, immunomodulation regimen, disease biology, and human physiology.

In conclusion, we present a risk register that can serve as a resource for mitigating risk and driving productivity for the development of future AAV-based gene therapies, which will be useful for researchers, drug developers, physicians, and patients.

Scientific Focus Area: Molecular Pharmacology

This page was last updated on Tuesday, August 6, 2024