In this presentation, Raiko Stephan, Therapeutic Area Biomarker Lead at Novartis, covered several key points regarding the role and applications of biomarkers in drug development and gene therapy. He began by introducing biomarkers, the measurable characteristics indicating normal physiological responses or disease states in the body. Stephan explained how the FDA has categorised biomarkers into seven types, each used differently depending on context and intended use.
Stephan elaborated on the diverse applications of biomarkers, explaining how they were used to monitor treatment effects, such as enzyme activity in metabolic disorders. This information was crucial for making internal decisions during drug development. The presentation highlighted the challenges faced in developing gene therapies for rare diseases, particularly due to limited patient numbers and an incomplete understanding of the diseases, which has led to gaps in clinical development.
Safety concerns in gene therapy are also a significant part of the discussion. Stephan mentioned issues like hepatotoxicity and thrombocytopenia observed in clinical settings that were not always predicted by animal models. He emphasised this gap in translatability between animal models and human clinical settings, especially regarding hepatotoxicity and complement activation.
The presentation also covered the various applications of gene therapy, including gene replacement and gene silencing, with Adeno-Associated Viruses (AAVs) used as delivery vehicles for therapeutic transgenes. Evaluating gene delivery involved assessing the presence and expression of the transgene in target tissues and cells, along with its biological function.
Clinical feasibility was another important point, focusing on the availability of matrices and the ability to collect meaningful longitudinal data for evaluating treatment effects. Stephan stressed the importance of contextualising biomarkers and their intended use to make informed decisions in drug development and ensure the safety and efficacy of gene therapies.
Overall, Raiko Stephan's presentation provided a comprehensive overview of the current state and challenges of biomarkers and gene therapy, leaving the audience with a deeper understanding of these critical aspects in modern medicine.
