The Critical Role of Bioanalysis in AAV Therapies
Specialized bioanalysis drives AAV therapies, ensuring safety, gene expression tracking, and robust clinical translation for gene therapies.
Gene therapy has evolved since the first drug was approved in 2004. Since then, AAV therapies have gained traction in the gene therapy market with the first approved AAV-based drug in 2013. With these new modalities, the need for specialized bioanalytical support becomes increasingly critical, and relies on traditional and non-traditional assays. These assessments are crucial for understanding the vector’s safety profile and therapeutic potential.
This webinar will explore the expanding role of bioanalysis in AAV therapies, focusing on biodistribution, transgene expression, immunogenicity, and ELISpot. With AAVs becoming more niche, there is a growing demand for detailed analysis to understand their safety profiles and their broader applications across different therapeutic areas. This discussion will highlight the significant contributions of bioanalytical methods to the development of AAV therapies, touch on important regulatory recommendations on assay validation, and explore how to approach these methods to be successful.
What will you learn?
- Understanding bioanalysis for AAV therapies: Learn how bioanalytical methods like qPCR, LBA, and immunohistochemistry are used to evaluate biodistribution, transgene expression, and immunogenicity.
- Safety and efficacy in preclinical studies: Gain insights on how adverse effects, gene expression, and off-target impacts are monitored to predict human responses and guide dose selection.
- Expanding role of bioanalysis in gene therapy: Discover how bioanalysis supports emerging therapeutic applications as AAV therapies become more niche and complex.
- Comprehensive techniques for clinical translation: Explore how qPCR, ELISpot, and LBA assessments contribute to the successful transition from laboratory studies to clinical trials.
- Advanced therapeutic applications: Learn the importance of detailed analysis for assessing the broader safety profiles of AAV therapies across different therapeutic areas.
This webinar was created and published by Bioanalysis Zone
About the Presenters
Catherine Spickler
Associate Director, Immunology
Charles River
John Cook
Senior Principal Research Scientist, Immunology, Bioanalysis & Biomarkers
Charles River
Read the Q&A
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In AAV-based gene therapy trials and clinical use, what immunogenicity assay provides the most critical data for patient selection, anti-capsid TAb or NAb?
The NAb data offers the greatest value as pre-existing NAb may impact the efficacy of the therapeutic being offered to the patient, something which may influence both the clinicians and the patients decision in regards to inclusion in the trial.
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As there are no specific guidelines yet for qPCR or ELIspot based bioanalysis of AAVs, which guidelines do one refer for these AAV therapeutic molecules ? How valid are they?
(ELISpot)ICH M10 guidance considered and followed where possible, in addition CRL subject matter experts from all CRL sites have collaborated to development and implement best scientific practices for the validation of these methods.
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Is the FDA consistently requesting ELISPOT immunogenicity safety data for Ph1/2 AAV clinical studies, despite the known challenges around the assay such as PBMC quality, and unclear correlation with clinical outcomes?
CRL continue to see increased requests for ELISPOT work, however, this is not necessarily the result of regulatory requests but something the client has a desired to explore. The use of stringent acceptance criteria in regards to minimum viability of PBMC helps to mitigate concern over quality.
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Would you still recommend conducting either ELISPOT or Flow assay to evaluate AAV immunogenicity in clinical studies where timelines for PBMC isolation and cryopreservation from collection, span between 24-48 hrs or longer?
Both options do present challenges in regards to sample stability, these challenges need to be understood through careful and considered method validation. In addition, an increasing number of clinical centers are proficient in the preparation and freezing of PBMC samples.