2023 FDA Updates:


8:30 am  KEYNOTE PRESENTATION: Immunogenicity Assessment of Gene Therapy Products
Anurag Sharma, PhDAnurag Sharma, PhD, Gene Therapy Reviewer, CBER, FDA
Despite great promise, the immunogenicity of gene therapies remains one of the biggest challenges. Immunogenicity can impact the safety, efficacy, and long-term durability of gene therapies. Addressing immunogenicity-associated challenges is critical to realizing the full potential of these life-saving therapies. In my talk, I will discuss FDA’s perspective on the immunogenicity associated with gene therapies.


8:30 am Clinical Pharmacology Evaluations of Immunogenicity Impact – Towards Harmonization and Best Practices
Yow-Ming Wang, PhDYow-Ming Wang, PhD, Associate Director for Biosimilars and Therapeutic Biologics, CDER, FDA
Immunogenicity developed against therapeutic biologics is undesirable and can have serious clinical consequences. To address the concern of negative impact of immunogenicity on treatment effects, therapeutic drug monitoring has been adopted as a mechanism of patient management in some clinical specialties. Advances in leveraging clinical pharmacology data have offered an option for evaluating clinical impacts and contribute the considerations of therapeutic drug monitoring. With available and emerging methodologies in the clinical pharmacology evaluations of immunogenicity impact, forward planning towards harmonization and developing best practice is essential. This presentation will discuss the current challenges and potential future directions based on the review experience in the Office of Clinical Pharmacology at the FDA.

12:30 pm  KEYNOTE PRESENTATION: Immune Responses to Cas9 and Emerging Cas Proteins Derived from Diverse Microorganisms
Zuben Sauna, PhDZuben Sauna, PhD, Research Biologist, CBER, FDA
Immunogenicity refers to immune responses to proteins used in therapeutic applications. Immunogenicity is of concern during drug development and licensure as it can affect the safety and/or efficacy of drug products. The presentation will provide: (1) An overview of T and B cell responses to Cas9 proteins which are derived from human pathogens. (2) Compare the immune responses to Cas9 to those from novel Cas proteins which are derived from archaea and bacteriophage. Judicious application of immunogenicity risk-assessment and comparative studies of different Cas proteins could potentially help make in vivo gene editing safer.


11:30 am  Differential Immune Responses to Deamidated Adeno-Associated Virus Vector
Ronit Mazor, PhDRonit Mazor, PhD, Principal Investigator, CBER, FDA
Adeno-associated viruses (AAV) are potent vectors used for gene therapy, but recent clinical findings have revealed immunogenicity-related challenges, including formation of a cytotoxic immune response against AAV capsid protein in transfected cells. We report that deamidation, a spontaneous post-translational modification that occurs in multiple AAV serotypes, can result in formation of CD4 T cell epitopes with a Th1 cytokine pattern in donor samples with specific HLA backgrounds.

3:15 pm Assessing Immunogenicity Using Immune Humanized Mice
Kristina-HowardKristina Howard, PhD, Principal Investigator, Division of Applied Regulatory Science (DARS), CDER, FDA