Angioedema is characterized by a sudden soft tissue swelling (an “attack”) that may occur everywhere in the body, sometimes at several anatomical locations, and usually lasts for a few days. Angioedema attacks in the abdomen may cause excruciating pays and attacks of the laryngeal area may be lethal because of asphyxiation. Persons with a chronic form of this disease suffer from multiple attacks, with attack frequencies ranging from once a year to once a week. Several forms of angioedema are recognized: hereditary angioedema, caused by deficiency of the blood protein C1-inhibitor; angioedema associated with urticaria, which has an allergic basis; drug-induced angioedema which particularly is seen with ACE inhibitors; angioedema associated with auto-immune and other diseases; and idiopathic angioedema when no obvious cause is found.
Chronic idiopathic angioedema occurs in 1 of 2,000 people. Currently, no effective treatment of this disease is available, anti-allergic drugs have no effect in idiopathic angioedema. The disease can have an enormous impact on the quality of life and when localized in the throat also can be life threatening.
Angioedema is caused by an increase of vasopermeability, which results in the accumulation of extravascular fluid in the soft tissues. The proteins prekallikrein, high-molecular weight kininogen (HK), FXI and FXII together constitute the so called “contact system”. As the name suggests, this system becomes activated upon contact of blood with artificial surfaces. Importantly, during activation bradykinin is released. Bradykinin increases vascular permeability, with oedema as a result. Several studies recently have provided compelling evidence that bradykinin mediates angioedema.
Prothix is developing a monoclonal antibody, PRO-04, that blocks the formation of bradykinin. PRO-04 can be used for prophylaxis as well as for on demand therapy. Considering its anticipated half-life (2-3 weeks in humans), a single injection of PRO-04 in an acute angioedema attack is expected not only to cure the acute attack, but also to provide prophylaxis during the subsequent 3-6 weeks for a new angioedema attack. PRO-04 likely is effective for all forms of angioedema. However, Prothix intends to develop PRO-04 first for chronic idiopathic angioedema since there is an urgent unmet medical need for effective treatment of this disabling disease.