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?