Over the last two decades, studies on gene therapy for hemophilia A and B have been performed and they are currently in phase III of clinical development. The overall goal of gene therapy for hemophilia A and B is to provide patients with functional factor VIII and factor IX genes capable of producing the respective proteins (FVIII/FIX). Theoretically, this may be achieved by gene transfer, whereby genetic material is delivered using viral vectors or non-viral means, or by gene repair/editing, in which the causative mutations are identified and subsequently corrected. For gene transfer, the following vectors have been used: non-viral vectors, retroviral vectors, adenoviral vectors, lentiviral vectors, and adeno-associated viral vectors. The most used vectors with the best clinical results have been achieved with adeno-associated viral vectors. Adeno-associated virus (AAV) is a non-enveloped parvovirus which shows widespread infection in the human population, and yet is not associated with any pathogenic disease. The genome of these viruses can be replaced with an expression cassette for a therapeutic protein. These recombinant AAV (rAAV) vectors are engineered in such a way that durable expression of the therapeutic protein is achieved. Moving from protein replacement to gene replacement overcomes many of the unmet challenges to hemophilia care. Gene therapy can result in endogenous expression of the needed clotting factor leading to steady state levels higher than possible with replacement therapy and a sustained duration of action. This would liberate individuals from prophylaxis and the need for regular intravenous infusions, eliminating the overall burden of treatment and removing the problems of therapy compliance. In addition, a curative approach will lead to large cost savings for the patient and the healthcare system, which is increasingly necessary as healthcare spending continues to outpace economic growth on an unsustainable path.
These same vectors and techniques can be used to cure the rarest of bleeding disorders, such as FVII and FX deficiency, which can affect just a few dozen people or less in a particular country. However, due to the high clinical developmental costs and small market opportunity, no commercial company has been interested in developing gene therapy for FX or any of the other rare bleeding disorders. Furthermore, experts agree that it will probably take another 10 to 20 years before gene therapy will be largely available in the developing world, and recent actions by the leaders of gene therapy in hemophilia A and B support this prediction. The main reason for the long timeframe before gene therapy will be available in low income countries is the estimated cost for gene therapy lies between 800,000 and 2,000,000 dollars per treatment. This high price is prohibitive to developing countries, and so their patients will not have access to treatments that would best boost their health and even reduce long term healthcare costs for these patients. Closing the treatment gap between patients in the developed and developing world remains an unmet ethical imperative, one in which SanaGen is uniquely created to address.