Ecallantide for treatment of acute attacks of hereditary angioedema

The pharmacology, pharmacokinetics, efficacy, safety, dosage, administration, adverse effects, and place in therapy of ecallantide, a kallikrein inhibitor for the treatment of hereditary angioedema (HAE), are reviewed.

Ecallantide is the first member of the kallikrein inhibitor class approved for the treatment of acute attacks of HAE. Ecallantide works by binding to kallikrein, preventing the conversion of kininogen to bradykinin, which reduces vascular permeability, thus reducing the swelling associated with acute attacks of HAE. Ecallantide has been studied for the treatment of HAE in three Phase II studies and two Phase III studies. These studies were collectively known as the EDEMA (Evaluation of DX-88's Effect in Mitigating Angioedema) studies. Phase III clinical trials found that ecallantide is superior to placebo in ameliorating patient symptoms associated with acute attacks of HAE at any anatomical site. Ecallantide has a favorable safety profile, with the most common adverse effects being gastrointestinal effects, headache, and injection site reactions. The most severe adverse effects of ecallantide are the risk of anaphylaxis and the possible development of antiecallantide antibodies. A risk evaluation and mitigation strategy program has been approved by the Food and Drug Administration to help ensure the safety and efficacy of ecallantide use. The recommended dose is 30 mg given as three separate subcutaneous injections.

Ecallantide is a novel agent approved for the treatment of acute attacks of HAE at any anatomical site. It is one of only three medications approved for this indication in the United States, presents a unique mechanism of action, and appears to be safe and effective when used for its labeled indication.