This session will focus on the latest progress in hemophilia gene therapy to achieve durable factor expression without immunogenicity, practical strategies that use patient-tailored pharmacokinetics to optimize prophylaxis, and novel non-factor therapeutics that target clot inhibitors to promote hemostasis.
Dr. Lindsey George will provide an overview of progress in gene therapy, including vector capsid efficiency, gene expression cassettes, and therapeutic factor VIII and IX expression. Approaches that have been successful in improving the level and durability of expression while avoiding liver toxicity and vector capsid immune response will be reviewed.
Dr. Alfonso Iorio will discuss the rationale for using pharmacokinetics to individualize prophylaxis regimens for patients with hemophilia. With the recognized variability in bleeding phenotype, even in patients with the same factor level, a practical strategy that tailors prophylaxis regimens to individual physical activity and pharmacokinetic handling of factor will be reviewed.
Dr. Margaret Ragni will focus on novel non-factor therapies that inhibit clot inhibitors (e.g., antithrombin and tissue factor pathway inhibitors) or render clotting factors resistant to regulatory clot inhibitors to achieve hemostasis in hemophilia patients with and without inhibitors. Their mechanisms of action, safety and efficacy profiles, and effects on thrombin generation will be reviewed.