Hereditary angiodema: a current state-of-the-art review, VI: novel therapies for hereditary angioedema.
OBJECTIVE
To provide a comprehensive overview on clinical trial design and results of emerging therapies for the treatment of hereditary angioedema (HAE).


METHODS
MEDLINE or PubMed literature searches were conducted to identify double-blind, placebo-controlled trials investigating C1 esterase replacement, kallikrein inhibitor, and bradykinin receptor 2 antagonist therapies.


METHODS
Ongoing trials or those just recently completed from all companies developing a product for the treatment of HAE are discussed.


RESULTS
All of these agents are believed to be effective when tested in patients in phase 1 or phase 2 trials. The studies have many features in common, including being placebo-controlled and blinded; having a preliminary screening visit at which the diagnosis is confirmed; having either low circulating C1 inhibitor protein levels or low levels of functional C1 inhibitor, low C4 levels, and normal C1q levels; enrolling individuals who are relatively early in attacks (4-6 hours from the onset); and stipulating that patients continue taking the medications that they have been taking in the long term. The type of attack acceptable for each treatment protocol varies from study to study. Some allow peripheral edema attacks, some facial attacks, and in some studies, the Food and Drug Administration has allowed purified serum C1 inhibitor to be used as a rescue medication if the patient remains in difficulty after the study drug has been used and found to be ineffective.


CONCLUSIONS
The outlook for new, effective short-term therapy appears to be excellent. In the near future, a whole new therapeutic armamentarium to care for patients with HAE should be available in the United States.
Frank
Michael M
MM
Department of Pediatrics, Duke University School of Medicine, Durham, NC 27710, USA. frank007@mc.duke.edu
D054179:Angioedemas, Hereditary / Q000188:drug therapy* / Q000276:immunology; D000818:Animals; D030801:Animals, Genetically Modified / Q000378:metabolism; D001920:Bradykinin / Q000031:analogs & derivatives / Q000627:therapeutic use; D065168:Bradykinin Receptor Antagonists; D002986:Clinical Trials as Topic; D003174:Complement C1 Inactivator Proteins / Q000096:biosynthesis / Q000627:therapeutic use; D050718:Complement C1 Inhibitor Protein / Q000627:therapeutic use; D015922:Complement C1q / Q000032:analysis; D003181:Complement C4 / Q000032:analysis; D004311:Double-Blind Method; D006801:Humans; D007275:Injections, Intravenous; D007279:Injections, Subcutaneous; D007610:Kallikreins / Q000037:antagonists & inhibitors / Q000627:therapeutic use; D011817:Rabbits; D018002:Receptors, Bradykinin / Q000627:therapeutic use; D011994:Recombinant Proteins / Q000096:biosynthesis / Q000627:therapeutic use; D014481:United States
D065168:Bradykinin Receptor Antagonists; D003174:Complement C1 Inactivator Proteins; D050718:Complement C1 Inhibitor Protein; D003181:Complement C4; D018002:Receptors, Bradykinin; D011994:Recombinant Proteins; C065679:icatibant; D015922:Complement C1q; D007610:Kallikreins; D001920:Bradykinin