Ecallantide (DX-88) for acute hereditary angioedema attacks: Integrated analysis of 2 double-blind, phase 3 studies

• Published in: Journal of allergy and clinical immunology 2011-07, Vol.128 (1), p.153-159.e4
• Main Authors: Sheffer, Albert L., MD, Campion, Marilyn, MS, Levy, Robyn J., MD, Li, H. Henry, MD, PhD, Horn, Patrick T., MD, PhD, Pullman, William E., MD
• Format: Article
• Language: English
• Subjects: Acute Disease; Adult; Aged; Allergic diseases; Allergy and Immunology; Angioedema; Angioedemas, Hereditary - drug therapy; Biological and medical sciences; Child; Double-Blind Method; Drug dosages; Drug therapy; Ecallantide; Evaluation of DX-88’s Effects in Mitigating Angioedema 3 and 4; Female; Fundamental and applied biological sciences. Psychology; Fundamental immunology; hereditary angioedema; Humans; Immunopathology; Male; mean symptom complex severity; Medical sciences; Middle Aged; Patients; Peptides - therapeutic use; Plasma; plasma kallikrein inhibitor; Sarcoidosis. Granulomatous diseases of unproved etiology. Connective tissue diseases. Elastic tissue diseases. Vasculitis; Skin allergic diseases. Stinging insect allergies; Studies; Treatment Outcome; treatment outcome score; Young Adult
• ISSN: 0091-6749; 1097-6825
• DOI: 10.1016/j.jaci.2011.03.006

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.