Pharma industry sees US FDA human gene therapy for neurodegenerative diseases to propel new treatment options

Bengaluru, November 12, 2022:

Pharma industry sees that the US FDA guidance on human gene therapy for neurodegenerative diseases will help to propel new treatment options. It focuses on factors to be considered for product development, preclinical testing, and clinical trial design.

The final guidance provides recommendations to sponsors developing human gene therapy (GT) products for neurodegenerative diseases affecting adult and pediatric patients. Neurodegenerative diseases are disorders known for progressive degeneration of the structure and function of the central nervous system or peripheral nervous system. These diseases vary in prevalence, diagnosis, and management, and include genetic as well as age-related diseases. Now guidance finalizes the draft norms of January 2021.

Treatment of neurodegenerative diseases may include the use of gene therapy products, such as viral vectors. The considerations for product manufacturing, testing and release of GT products for neurodegenerative diseases are the same as those for other GT products. However, some aspects of GT products for neurodegenerative diseases, such as challenges associated with the route of administration, volume of product that can be administered, the delivery device, and the study population size.

Typically, critical quality attributes (CQAs) of an investigational drug product are evaluated during each phase of clinical development, and characterization data from multiple drug product lots are correlated to clinical outcomes.

Early-phase clinical studies of neurodegenerative diseases involving small study populations, in addition to focusing on safety assessments, also provide early evidence on effectiveness. In addition, innovative manufacturing strategies such as the production of multiple small lots versus a single large product lot may be considered to increase manufacturing process experience and product knowledge.

Gene therapy products may have quality attributes with higher variability than small molecule drugs or well-characterized biological products, and sponsors should consider additional product characterization studies to establish acceptance limits for the critical quality attributes.

Products used to treat neurodegenerative diseases may have to be administered in small volumes to sites of the disease or condition, such as the brain or spinal cord. These sites also have reduced clearance of the administered product, and final product volume and formulation are important considerations. Product critical quality attributes may also influence the final formulation parameters, and decisions regarding these product aspects may need to be made early in the manufacturing process development. Therefore, the global regulatory authority recommends that assays for evaluating product quality attributes be implemented early in product development and qualified as accurate, precise, sensitive, and specific).

Sponsors developing GT products for neurodegenerative diseases are strongly encouraged to contact the Office of Tissues and Advanced Therapies (OTAT) in the Center for Biologics Evaluation and Research (CBER) prior to submitting an investigational new drug application. Design of gene therapy products should be based on current scientific knowledge and an evaluation of potential risks posed by the product to study subjects.

Moreover gene therapy products may induce unintended immune responses against host cells, become latent in neuronal tissues, or cause unwanted gene expression. We recommend that all GT products for neurodegenerative diseases be designed to reduce unintended immune responses. Drug product purity should be carefully evaluated early in product development. Purity assessment generally includes the evaluation of residual product-related impurities and process-related impurities product-related impurities in GT viral vector-based products used to treat neurodegenerative conditions include empty and wild-type viral particles, and replication-competent viruses.Pharmabiz