Ecallantide (DX-88), a plasma kallikrein inhibitor for the treatment of hereditary angioedema and the prevention of blood loss in on-pump cardiothoracic surgery

Expert Opin Biol Ther. 2008 Aug;8(8):1187-99. doi: 10.1517/14712598.8.8.1187.

Abstract

Background: Plasma kallikrein plays a major role in the contact (kallikrein-kinin) cascade producing bradykinin. Bradykinin is a vasodilator, which increases vascular permeability, activates inflammation and produces pain. Plasma kallikrein is also crosslinked to the coagulation system and the complement cascade.

Objective: Ecallantide (DX-88) is a potent and specific inhibitor of plasma kallikrein. Ecallantide is a recombinantly produced and engineered small protein based on the first Kunitz domain of human tissue factor pathway inhibitor. It was identified through phage display technology.

Methods: The search terms 'ecallantide', 'DX-88' and 'hereditary angioedema' were entered into Pubmed/Medline, ClinicalTrials and Google.

Results/conclusion: At present, the drug is being studied for two major indications. First, the results for the treatment of hereditary angioedema are promising. Second, a prospective randomised multi-centre trial for the reduction of blood loss during on-pump cardiothoracic surgery will be terminated in October 2008.

MeSH terms

  • Angioedemas, Hereditary / drug therapy*
  • Blood Loss, Surgical / prevention & control*
  • Cardiac Surgical Procedures / adverse effects*
  • Clinical Trials as Topic
  • Humans
  • Kallikreins / antagonists & inhibitors*
  • Peptides / pharmacology
  • Peptides / therapeutic use*
  • Serine Proteinase Inhibitors / pharmacology
  • Serine Proteinase Inhibitors / therapeutic use*

Substances

  • Peptides
  • Serine Proteinase Inhibitors
  • ecallantide
  • Kallikreins