Policy & Advocacy

Navigating Challenges in AAV Gene Therapy: A Preview of the FDA-Partnered Workshop

Andrew Liermann - December 03, 2024

The upcoming Class Considerations on Immunogenicity for AAV Gene Therapy Products workshop on Jan. 22 and 23 will address some challenges facing the class of AAV gene therapies.

The field of adeno-associated virus (AAV) gene therapies stands at a crossroads. In many cases they hold the promise to deliver groundbreaking advancements for previously untreatable conditions. There are, however, significant scientific, regulatory, and logistical hurdles that must be overcome in order to reach that outcome. ASGCT is excited to partner with FDA to discuss how to ensure science and patient safety stay at the forefront of regulatory innovation. The upcoming Class Considerations on Immunogenicity for AAV Gene Therapy Products workshop on Jan. 22-23, 2025, will address some of those challenges facing the class of AAV gene therapies. The Agency has contributed to the planning of topics and will host leading voices from FDA, academia, and industry to foster discussion and propose solutions that will shape the future of these products.

One of the critical topics that researchers and sponsors are wrestling with is immunogenicity in AAV gene therapy. Preexisting immunity, driven by neutralizing and binding antibodies, remains a key obstacle to broader patient access because it can disqualify patients from clinical trials or reduce the effectiveness of therapies. Additionally, inconsistencies in assay validation and the lack of standardized cutoffs make it difficult to accurately identify eligible patients, leading to variability in trial design and patient selection criteria. This further narrows the pool of participants and slows the pace of clinical development, ultimately delaying the availability of therapies for those in need.

Another focus area for the workshop will be the integration of clinical and preclinical data. Regulatory and research communities have long grappled with translating preclinical models into reliable predictors of human outcomes. Preclinical studies often fall short of replicating clinical toxicity, delaying the pathway to safe and effective therapies. By evaluating ways to align preclinical models with clinical data, presenters will delve into how to refine study designs and regulatory standards, ensuring more robust predictive power in AAV research.

The use of animal models for AAV development presents its own set of challenges. Limited resources, such as the shortage of non-human primates (NHPs), and the inherent difficulties in mimicking human immune responses create significant barriers. This session will not only identify these pain points but also examine innovative alternatives that could reshape how AAV therapies are tested and developed, addressing long timelines and resource constraints.

Lastly, the event will tackle strategies for overcoming neutralizing antibodies and discuss immunosuppression approaches in AAV therapies. Neutralizing antibodies are a significant barrier to redosing, as they can render subsequent treatments ineffective or increase the risk of adverse reactions. Similarly, variability in immunosuppression protocols can impact the safety and efficacy of treatments, particularly in patients who require repeat dosing due to the progressive nature of their conditions or limitations in initial dosing strategies.

As the gene therapy field continues to evolve, workshops like this one are vital to overcoming the scientific and regulatory barriers that hinder progress. By fostering collaboration among researchers, industry leaders, and regulatory experts, the event aims to pave the way for innovative solutions that can bring AAV gene therapies to more patients in need. Stay tuned for further updates and insights as we approach this pivotal event – and be sure to register today!

Andrew is ASGCT's Regulatory Affairs Manager.

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