The Hope of Gene Therapy
While the life expectancy of people with hemophilia is near normal, it is not normal.15 Joint bleeding has been reduced, but not eliminated.6, 9-14ABRs are approaching zero, but not zero.9-14,16,17 The burden of treatment has been drastically reduced but persists. Treatments are not accessible to large populations of patients and where they are, patients do not always adhere to recommended treatments.19 The risk of transmitting infectious agents or other manufacturing mishaps remains.20 Emicizumab may increase the risk of thrombotic events.21 The financial costs of treatment remain substantial. In short, there remains room for improvement in the treatment of hemophilia. Current gene therapy regimens may fulfill that need. A one-time treatment with rAAV vectors has resulted in hemostatic levels for both factor VIII and IX.1,2. Long term data is still needed, but current rAAV gene therapy may further reduce or eliminate joint disease and other bleeding complications. Although the financial cost of gene therapy is substantial, if hemostatic levels are sustained, the lifetime costs of treatment will be reduced.22 The most significant side effect of rAAV gene therapy for hemophilia during clinical trials has been mild liver inflammation, which has generally been controlled with steroids.1,2 Although the specter of genotoxicity has been raised, none has been observed to date in human trials of rAAV for hemophilia. Thus, it has been claimed that it is time to “prepare the way” for hemophilia gene therapy.23 Or is it?