The most used vectors with the best clinical results have been achieved with adeno-associated viral vectors, which is SanaGen’s current focus because of several advantages in clinical understanding/experience, cell targeting ability, safety (non-integrating) and efficacy. 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 care for hemophilia and other bleeding disorders. 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, 24 hours a day, 7 days a week, 365 days a year. 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, as populations age.
For over two decades, studies on gene therapy for hemophilia A and B have been performed and they are currently in phase III of clinical development, with the first approval expected by the end of 2022. By capitalizing on this knowledge, SanaGen is able to efficienctly and cost effectively develop new rare bleeding disorder therapies for unexplored markets.