Hereditary angioedema (HAE) is a rare and potentially life-threatening genetic condition that occurs in approximately 1 in 50,000 people. HAE patients are susceptible to sudden and prolonged attacks of edema, which often occur in the hands, feet, face, gastrointestinal tract, and airway. Attacks can result in severe swelling and pain, airway blockage, and nausea. Airway swelling is particularly dangerous and can lead to death by asphyxiation.
HAE patients have a defect in the gene for C1-inhibitor, the endogenous inhibitor of plasma kallikrein. C1-inhibitor deficiency enables attacks of uncontrolled plasma kallikrein activity and elevated levels of bradykinin, which lead to the increased permeability of blood vessels and release of fluid into surrounding tissue.
Treatment of HAE consists of prophylaxis, management of acute attacks and prophylactic therapy in situations where attacks may occur, such as minor surgery.
Commercially available treatment limitations include invasive routes of drug administration (eg, injection/infusion), inconvenient dosing regimens, poor efficacy, or undesired side effects. A best-in-class, oral small molecule plasma kallikrein inhibitor may provide an effective and more convenient way to manage HAE and improve quality of life.