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).

DATA SOURCES: 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.

STUDY SELECTION: 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.

CONCLUSION: 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.