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 (swelling), which often occur in the hands, feet, face, gastrointestinal tract, and airway resulting in severe swelling and pain, airway blockage, and nausea. Depending on the severity of the disease, some people will have many attacks each month, while others may go months without an attack.
HAE most commonly occurs as a result of insufficient levels or function of a protein called C1 esterase inhibitor (C1-INH), the naturally occurring inhibitor of the plasma kallikrein enzyme. C1-INH deficiency enables uncontrolled plasma kallikrein activity leading to elevated levels of bradykinin, which acts at the bradykinin B2 receptor resulting in increased permeability of blood vessels and release of fluid into surrounding tissue.
Treatment of HAE consists of long-term prophylaxis, management of acute attacks, and intermittent episodic prophylaxis in advance of known triggers. Multiple therapies are available to patients, acting at different points in the enzymatic/signaling pathway. Only one approved therapy, icatibant, acts directly at the bradykinin B2 receptor to treat all types of HAE by blocking the bradykinin signal. Clinical experience with icatibant demonstrates that intervention at the B2 receptor modulates all signs and symptoms of HAE. The Pharvaris team is drawn from the core team that originally invented and developed icatibant.
All current therapies, including icatibant, are limited by invasive routes of drug administration (injection or infusion), inconvenient dosing regimens, or undesired side effects. Surveys of patients with HAE overwhelmingly show that they seek additional treatment options. A first-in-class, oral small-molecule antagonist of the bradykinin B2 receptor may provide an effective and more convenient way to manage HAE and improve quality of life.