Ecallantide for the Treatment of Hereditary Angiodema in Adults

Abstract

Hereditary angioedema (HAE) is a clinical disorder characterized by a deficiency of C1 esterase inhibitor (C1-INH). HAE has traditionally been divided into two subtypes. Unique among the inherited deficiencies of the complement system, HAE Types I and II are inherited as an autosomal dominant disorder. The generation of an HAE attack is caused by the depletion and/or consumption of C1-inhibitor manifested as subcutaneous or submucosal edema of the upper airway, face, extremities, or gastrointestinal tract mediated by bradykinin. Attacks can be severe and potentially life-threatening, particularly with laryngeal involvement and treatment of acute attacks in the United States has been severely limited. In December 2009 the FDA approved ecallantide for the treatment of acute HAE attacks. Ecallantide is a small recombinant protein acting as a potent, specific and reversible inhibitor of plasma kallikrein which binds to plasma kallikrein blocking its binding site, directly inhibiting the conversion of high molecular weight kininogen to bradykinin. Administered subcutaneously, ecallantide was demonstrated in two clinical trials, EDEMA3 and EDEMA4, to decrease the length and severity of acute HAE attacks. Although there is a small risk for anaphylaxis, which limits home administration, ecallantide is a novel, safe, effective and alternative treatment for acute HAE attacks.

Angioedema: Etiology, Pathophysiology, Current and Emerging Therapies

“…Potentially serious hypersensitivity reactions, including anaphylaxis, occurred in 2.7% of patients receiving subcutaneous ecallantide (4,17). All cases of anaphylaxis occurred within 1 h of administration.…”

“…Type I is characterized by low levels of C1-INH and accounts for 80%À 85% of cases (17). Normal levels and decreased function of C1-INH are seen in type II HAE, which accounts for most of the remaining 15%À20% of cases (17,18). A third type of HAE (type III) with normal levels and normal function of C1-INH has been described, primarily in women (19).…”

“…Type I is characterized by low levels of C1-INH and accounts for 80%À 85% of cases (17). Normal levels and decreased function of C1-INH are seen in type II HAE, which accounts for most of the remaining 15%À20% of cases (17,18).…”

“…HAE consists of three subtypes (17). Type I is characterized by low levels of C1-INH and accounts for 80%À 85% of cases (17).…”

Hereditary angioedema: what the gastroenterologist needs to know

“…Ecallantide (Kalbitor ® ; Dyax Corp, Burlington, MA, USA) is a recombinant protein, synthesized in yeast, that is a potent, specific, and reversible inhibitor of plasma kallikrein 65,66. Ecallantide binds to plasma kallikrein and directly inhibits conversion of high-molecular-weight kininogen to bradykinin 65.…”