The Future of Hemophilia Treatment: Longer-Acting Factor Concentrates versus Gene Therapy

Abstract

Gene therapy is the only novel technology that currently offers the prospect of a lasting cure for hemophilia and freedom from the burden of repeated injections. Recent data from a handful of patients who have undergone gene therapy for hemophilia B are very encouraging with a sustained factor IX (FIX) level of 0.05 IU/mL maintained for over 4 years. While this level is above the current usual target trough levels, it falls well short of the level that patients on prophylaxis with longer-acting products can expect. Prophylaxis is also associated with high peak levels, which permits patients to maintain an active lifestyle. A major barrier to widespread adoption of gene therapy is a high seroprevalence of antibodies to adeno-associated virus (AAV) vectors in the general population. Young children would be the best candidates for gene therapy in view of much lower seroprevalence to AAV in infants. A stable level of FIX early in life would prevent the onset of joint bleeds and the development of arthropathy. The recent experience with apolipoprotein tiparvovec (Glybera; uniQure, Amsterdam, the Netherlands) indicates that gene therapy is unlikely to prove to be a cheap therapeutic option. It is also quite possible that other new technologies that do not require viral vectors (such as stem cell therapy) may overtake gene therapy during development and make it redundant.