Abstract
Gene therapy has held promise to cure hemophilia since factor (F)VIII and FIX were cloned more than 40 years ago. However, scientific understanding of the adeno-associated virus, the predominant vector used in gene therapy, has been insufficient to overcome many of the hurdles encountered, resulting in failed clinical studies, marginal efficacy, unfavorable benefit/risk, or phase 3 studies that do not sufficiently support wide commercial use. However, a functional cure, defined as permanent factor levels of at least 40%, has seen durable success in some FIX gene therapy recipients. Less success has been seen for FVIII gene therapy. Additional reasons for slow commercial uptake include the need to establish complex reimbursement processes for very high-priced drugs.