title: Ecallantide (DX-88) for acute hereditary angioedema attacks: integrated analysis of 2 double-blind, phase 3 studies.
abstract: BACKGROUND
  Hereditary angioedema (HAE) is a rare disorder characterized by recurrent angioedema attacks. Ecallantide, a novel plasma kallikrein inhibitor, inhibits production of bradykinin, the key mediator of these angioedema attacks.
  
  
  OBJECTIVE
  We sought to further characterize the safety and efficacy of ecallantide for HAE attacks by performing an integrated analysis of pooled data from 2 phase 3 studies.
  
  
  METHODS
  An integrated analysis was conducted with data from 2 randomized, double-blind, placebo-controlled studies in which patients with HAE (age ≥10 years) received 30 mg of subcutaneous ecallantide or placebo within 8 hours of onset of a moderate-to-severe attack at any anatomic site. Efficacy was evaluated by using validated patient-reported outcome measures: the Mean Symptom Complex Severity (MSCS) score and the Treatment Outcome Score (TOS).
  
  
  RESULTS
  Compared with placebo, ecallantide resulted in significantly greater reduction in MSCS scores from baseline to 4 hours after dosing (ecallantide [mean ± SD], -0.97 ± 0.78; placebo, -0.47 ± 0.71; P < .001) and a significantly greater increase in TOSs at 4 hours (ecallantide, 55.5 ± 46.5; placebo, 20.0 ± 58.9; P < .001). Significantly greater symptomatic improvement over placebo occurred through 24 hours after dosing (MSCS score, P = .028; TOS, P = .039). Ecallantide demonstrated efficacy at all attack sites. The incidence of treatment-emergent adverse events was similar between groups.
  
  
  CONCLUSIONS
  This integrated analysis supports and expands on the results of the phase 3 studies. Ecallantide appears to be effective and well tolerated for the treatment of HAE attacks.
authors.affiliation: Brigham and Women's Hospital, Division of Rheumatology, Immunology, and Allergy, Harvard Medical School, Boston, MA 02467, USA. asheffer@partners.org
authors.forename: Albert L
authors.initials: AL
authors.lastname: Sheffer
authors.forename: Marilyn
authors.initials: M
authors.lastname: Campion
authors.forename: Robyn J
authors.initials: RJ
authors.lastname: Levy
authors.forename: H Henry
authors.initials: HH
authors.lastname: Li
authors.forename: Patrick T
authors.initials: PT
authors.lastname: Horn
authors.forename: William E
authors.initials: WE
authors.lastname: Pullman
mesh_terms: D000208:Acute Disease; D000328:Adult; D000368:Aged; D054179:Angioedemas, Hereditary / Q000188:drug therapy*; D002648:Child; D004311:Double-Blind Method; D005260:Female; D006801:Humans; D008297:Male; D008875:Middle Aged; D010455:Peptides / Q000627:therapeutic use*; D016896:Treatment Outcome; D055815:Young Adult
chemical_list: D010455:Peptides; C511194:ecallantide