In addition to the development of NextGen, GenX, and Opt AAV3 vectors for gene therapy of hemophilia (A & B) in adult patients, aaVective is also developing novel vectors and strategies to treat children with hemophilia. These strategies will subsequently be extended to include additional undisclosed human liver diseases.

What is Hemophilia?

Hemophilia is an X-linked bleeding disorder caused by a mutation in the gene for coagulation Factor VIII (hemophilia A) or Factor IX (hemophilia B). Hemophilia is further characterized as mild (5-50%), moderate (1-5%) or severe (<1%) based on the factor level in the plasma.

It is estimated that hemophilia is present in 1:5000 male births and that 20,000 people are currently living with the disease in the United States. Hemophilia A is four times more common than hemophilia B. Each year, approximately 400 males are born with hemophilia in the United States with the same number in Europe. The actual number of people living in the world with hemophilia is unknown, and estimates vary. The Hemophilia Federation of America estimates that 400,000 people live with hemophilia worldwide, while the World Federation of Hemophilia reported in its 2017 Annual Global Survey, with 91 % of the world’s population covered by reporting countries, that 196,706 people had hemophilia A and B.

Traditional Treatments, Newer Treatments and Remaining Challenges

Over the past 30 years, the primary treatment for patients with hemophilia has been administration of plasma products or recombinant products to replace clotting factor. Such clotting factor replacements are administered at the time of clinically evident bleeding and prophylactically in patents with moderate to severe forms of the disease to help curtail the propensity for damage caused by internal bleeding.

Hemophilia A is four times more common than hemophilia B. Approximately 75% of those with hemophilia A have the moderate to severe form of the disease requiring frequent administration of clotting factor replacement. 25-30% of those with severe hemophilia A and 1-5% of persons with severe hemophilia B develop antibodies, known as inhibitors, causing resistance to infused factor replacement. The treatment of hemophilia, when inhibitors are present, is more difficult and extremely costly due to the complications which frequently manifest with inhibitors. While treatment for a patient with the mild form of hemophilia A or B may cost $30,000 per year in the United States, treatment for a patient with the severe form of the disease, with inhibitors, reportedly can cost more than $1 million annually.

Newer treatments for hemophilia A and B have been brought to market over the last few years which are longer-acting than traditional products (e.g. Aprolix® and Elocate® –Biogen), requiring only 1 or 2 infusions per week. Genentech recently began marketing a monoclonal antibody, Hemlibra® (Emicizumab), to treat hemophilia A, with and without inhibitors, which only requires once a week administration. These newer treatments have been characterized as providing enhanced patient convenience, rather than providing increased clinical efficacy or lower complication rates. Moreover, since patients continue to require at least weekly administration, throughout their lifetime, the newer treatments pose similar cost challenges as do the older, standard therapies.

The New Paradigm: Cure, Not Treatment

Over the past five years, there has been dramatic increased interest in the potential promise of gene therapy to cure hemophilia, with multiple companies conducting R & D activities, including clinical trials. Most of these efforts utilize a first-generation AAV serotype to replace the defective gene responsible for deficient clotting factor production. Because of inherent limitations of those vectors, very large doses must be administered to achieve effect. aaVective proposes that its NextGen, GenX, and Opt AAV3 vectors will achieve greater transduction, with smaller dosages, and will therefore be safer and provide better results.

Imagine a child born with hemophilia, who, with the administration of a single dose of therapeutic agent, could avoid the lifelong health complications, treatment burdens and costs of their inherited disease. aaVective wants to welcome that child into this world by developing products utilizing more effective vectors to cure hemophilia.