Factor VIII Inhibitors

• Factor VIII also was known as an antihemophilic factor, is an essential blood-clotting protein. Factor VIII is produced outside the liver, in liver sinusoidal cells and endothelial cells across the body.
• This protein is mixed in the bloodstream in an inactive form and binds to another molecule (von Willebrand factor), prior to damage to blood vessels occur.
• In case of injury, coagulation factor VIII responses by getting activated and it separates from von Willebrand factor.
• An inhibitor is known to be a polyclonal high-affinity immunoglobulin G (IgG) that will be directed against the FVIII protein. IgG4 antibodies are more predominant, and this will do not fix complement.
• The formation of an FVIII inhibitor is called to be a T-cell dependent event that involves antigen-presenting cells, B- and T-helper lymphocytes.
• The antibodies in inhibitor patients can concurrently target multiple FVIII epitopes, and these epitope targeting can be changed over time.
• FVIII inhibitors are classified based on the kinetics and extent of inhibition into Type I inhibitors that are more common in severe hemophilia and Type II inhibitors that are common in inhibitor patients with mild hemophilia or in patients without hemophilia who got developed an acquired FVIII inhibitor.
• A total of 222 studies are under different stages of drug development in clinical trials of factor VIII inhibitors that are majorly applicable for treating hemophilia condition.
• Among them, 28 reviews are in phase 3 stage of drug development that includes drugs like turoctocog alfa, Emicizumab, Fitusiran (ALN-AT3SC), Rituximab, Cyclophosphamide are going very vast that will add to the development of market growth, and only less number of studies are under phase 2, phase 1, early phases of drug development that includes drugs like Bortezomib, BAY1093884, Concizumab, MOD-5014.
• Thus, more research and development of factor VIII inhibitors must be designed in order to increase market growth.
• FVIII inhibitors are interfering with the infused factor concentrates, thereby rendering them ineffective and necessarily making the use of most costly and less effective alternative hemostatic agents.
• Inhibitor development is currently coming under the most significant treatment complication in patients with hemophilia that is associated with substantial morbidity and a decreased quality of life.
• Thus, the development of an FVIII inhibitor is the result of a complex interaction between the patient’s immune system, environmental and genetic risk factors. The main goal of the treatment is the eradication of the inhibitor by immune tolerance.
• Some of the key factors responsible for the market growth are the growing incidence of hemophilia A, the increased adoption of prophylactic treatment, and the development of novel drugs with extended action.
• In addition to this, increasing demand for novel recombinant products with extended half-life, the introduction of plasma-derived products for recombinant factor VIII products at low costs, and the emergence of monoclonal antibodies and gene therapy drug products will also further drive the growth of the factor VIII inhibitors market.