EDEMA4: a phase 3, double-blind study of subcutaneous ecallantide treatment for acute attacks of hereditary angioedema.
BACKGROUND
Hereditary angioedema (HAE) is a genetic disorder resulting from low levels of C1-inhibitor activity that manifests as acute attacks of variable and sometimes life-threatening edema. Ecallantide is a novel potent inhibitor of human plasma kallikrein, a key mediator of the excessive formation of bradykinin associated with the signs and symptoms of an HAE attack.


OBJECTIVE
To evaluate the efficacy and safety of ecallantide in the treatment of acute HAE attacks.


METHODS
In this double-blind, placebo-controlled study, patients with a moderate to severe HAE attack were randomized 1:1 to receive 30 mg of subcutaneous ecallantide or placebo. The primary efficacy end point was change from baseline in mean symptom complex severity score 4 hours after dosing. Additional end points included treatment outcome score 4 hours after dosing and maintenance of significant overall improvement through 24 hours.


RESULTS
Ninety-six patients were enrolled. Mean (SD) change from baseline in mean symptom complex severity score 4 hours after dosing was significantly greater with ecallantide use (-0.8 [0.6]) compared with placebo use (-0.4 [0.8]) (P = .01 comparing distributions). Ecallantide therapy was also associated with a significantly larger mean (SD) treatment outcome score 4 hours after dosing vs placebo use (ecallantide: 53.4 [49.7]; placebo: 8.1 [63.2]; P = .003 comparing distributions). The benefit of ecallantide was apparent within 2 hours after dosing and was maintained through 24 hours after dosing. The safety profile was similar between the treatment groups.


CONCLUSIONS
Ecallantide appears to be an effective and safe treatment for acute attacks of HAE.
Levy
Robyn J
RJ
Family Allergy & Asthma Center PC, Atlanta, Georgia 30342, USA. levyr@familyallergycenter.com
Lumry
William R
WR
McNeil
Donald L
DL
Li
H Henry
HH
Campion
Marilyn
M
Horn
Patrick T
PT
Pullman
William E
WE
D000208:Acute Disease; D000293:Adolescent; D000328:Adult; D000368:Aged; D054179:Angioedemas, Hereditary / Q000188:drug therapy*; D004311:Double-Blind Method; D005260:Female; D006801:Humans; D007279:Injections, Subcutaneous; D008297:Male; D008875:Middle Aged; D010455:Peptides / Q000008:administration & dosage* / Q000009:adverse effects
D010455:Peptides; C511194:ecallantide