Hereditary angioedema: a current state-of-the-art review, VIII: current status of emerging therapies.
OBJECTIVE
To provide an overview on the current status of emerging therapies for hereditary angioedema (HAE) in the United States.


METHODS
Summary statements were obtained from each pharmaceutical company regarding their agent.


METHODS
Each agent is undergoing or has completed phase 3, double-blind, placebo-controlled trials.


RESULTS
Berinert P, a purified, virus-inactivated, human plasma-derived C1 inhibitor (C1-INH) concentrate, is being investigated in 2 international, multicenter, prospective trials. Experience with this agent in Europe and Canada indicates it is effective and safe. Cinryze is a nanofiltered C1-INH replacement therapy demonstrated to be effective and safe in acute and prophylactic arms of a phase 3, double-blind, placebo-controlled study. Rhucin, a recombinant human C1-INH replacement therapy from transgenic rabbits, has been shown to be effective and safe in phase 2 and phase 2/3 studies, with an additional phase 3 study ongoing. DX-88 or ecallantide, a potent and specific inhibitor of plasma kallikrein, achieved all primary and secondary efficacy end points in a placebo-controlled, double-blind, phase 3 study, with a second phase 3 study ongoing. Icatibant, a potent and specific peptidomimetic bradykinin 2 receptor antagonist, was studied in 2 phase 3 trials: FAST 1 (For Angioedema Subcutaneous Treatment) did not achieve statistical significance for the primary end point but did so for secondary end points, whereas FAST 2 achieved statistical significance for primary and secondary end points.


CONCLUSIONS
The future treatment of HAE in the United States appears promising based on progress being made in drug development for this orphan disease.
Bernstein
Jonathan A
JA
University of Cincinnati, Ohio, USA. Jonathan.Bernstein@uc.edu
D000319:Adrenergic beta-Antagonists / Q000627:therapeutic use; D054179:Angioedemas, Hereditary / Q000188:drug therapy*; D000818:Animals; D030801:Animals, Genetically Modified; D001288:Attention; D001920:Bradykinin / Q000031:analogs & derivatives / Q000627:therapeutic use; D017326:Clinical Trials, Phase III as Topic; D050718:Complement C1 Inhibitor Protein / Q000235:genetics / Q000302:isolation & purification / Q000627:therapeutic use; D018849:Controlled Clinical Trials as Topic; D005374:Filtration; D014943:Global Health; D006801:Humans; D007610:Kallikreins / Q000037:antagonists & inhibitors / Q000627:therapeutic use; D053758:Nanoparticles / Q000627:therapeutic use; D010455:Peptides / Q000627:therapeutic use; D011817:Rabbits; D011994:Recombinant Proteins / Q000096:biosynthesis / Q000627:therapeutic use; D016896:Treatment Outcome
D000319:Adrenergic beta-Antagonists; D050718:Complement C1 Inhibitor Protein; D010455:Peptides; D011994:Recombinant Proteins; C511194:ecallantide; C065679:icatibant; D007610:Kallikreins; D001920:Bradykinin