Current and Emerging Management Options for Hereditary Angioedema in the US

Abstract

Hereditary angioedema (HAE) is a rare disorder characterized by recurrent attacks of swelling that may involve multiple anatomical locations. In the majority of patients, it is caused by a functional or quantitative defect in the C1 inhibitor (C1-INH), which is an important regulator of the complement, fibrinolytic, kallikrein-kinin and coagulation systems. Standard treatments used for other types of angioedema are ineffective for HAE. Traditional therapies for HAE, including fresh frozen plasma, ε-aminocaproic acid and danazol, may be well tolerated and effective in some patients; however, there are limitations both in their safety and efficacy.

Several novel therapies have completed phase III trials in the US, including: (i) plasma-derived C1-INH replacement therapies (Berinert P® and Cinryze®); (ii) a recombinant C1-INH replacement therapy (conestat alfa; Rhucin®); (iii) a kallikrein inhibitor (ecallantide [DX-88]); and (iv) a bradykinin-2-receptor antagonist (icatibant). Both Berinert P® and Cinryze® are reported to have excellent efficacy and safety data from phase III trials. Currently, only Cinryze® has been approved for prophylactic use in the US. US FDA approval for other novel agents to treat HAE and for the use of Cinryze® in the treatment of acute attacks is pending.

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Fig. 1
Table I

Notes

  1. 1.

    The use of trade names is for identification purposes only and does not imply endorsement.

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Acknowledgements

We would like to thank Richard Bruns, RN, CRC, Christopher Codispoti, MD, Haejin Kim, MD, and Maziar Rezvani, MD, for taking active roles in conducting hereditary angioedema clinical trials at the University of Cincinnati. Tolly Epstein, MD, has served as a sub-investigator on clinical research studies for Pharming and Dyax. Jonathan Bernstein, MD, has served as a principal investigator for studies conducted by Lev, Pharming, CSL-Behring, Dyax and Jerini. No sources of funding were used to assist in the preparation of this review.

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Epstein, T.G., Bernstein, J.A. Current and Emerging Management Options for Hereditary Angioedema in the US. Drugs 68, 2561–2573 (2008). https://doi.org/10.2165/0003495-200868180-00003

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Keywords

  • Fresh Freeze Plasma
  • Danazol
  • Hereditary Angioedema
  • Icatibant
  • Ecallantide