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Blocking of Plasma Kallikrein Resolves Hereditary Angioedema Attacks 4 Hours Faster Than No Treatment: Presented at AAAAI

By Maggie Schwarz

PHILADELPHIA -- March 17, 2008 -- A double-blind, phase 3 trial has confirmed the efficacy versus placebo of treating attacks of hereditary angioedema (HAE), a finding reported here at the Annual Meeting of the American Academy of Allergy, Asthma, and Immunology (AAAAI 2008).

Robyn J. Levy, MD, Allergist, Family Allergy and Asthma Center, Section Chief, Department of Allergy, Children's Healthcare of Atlanta at Scottish Rite, Atlanta, Georgia, presented the findings on March 16.

Dr. Levy said there is currently no treatment option for HAE, a rare autosomal dominant disorder characterised by a deficiency of C1 esterase inhibitor (C1-INH), resulting in reduced inhibition of plasma kallikrein.

HAE affects approximately one in 10,000 to 50,000 persons worldwide. Patients suffer unpredictable, recurrent, potentially life-threatening acute attacks of oedema affecting the larynx, oropharynx, face, abdomen/intestinal tract, genitalia, or limbs. There are no disease-specific therapies available to treat acute HAE attacks.

The study -- called EDEMA3 -- was a 2-stage trial designed to evaluate ecallantide for moderate-to-severe attacks of HAE. In the double-blind stage, 72 patients were randomised in a 1:1 ratio to treatment with ecallantide 30 mg or placebo. The repeat-dosing stage enrolled 67 patients to assess the effect of open-label doses of ecallantide for subsequent attacks.

Of the 67 patients in the repeat-dosing, open-label stage, 22 ecallantide and 26 placebo patients also participated in the double-blind stage. The remaining 19 patients were enrolled directly in the repeat-dosing, open-label stage. The primary endpoint was mean treatment outcome score 4 hours postdosing. Secondary endpoints included mean symptom complex severity and time to improvement.

Improved response was seen at 4 hours (P = .02) and lasted through 24 hours (P = .03). Symptom severity decreased insignificantly from baseline to 4 hours (P = .02) and to 24 hours (P = .10).

Time to improvement and time to significant improvement were significantly shorter for ecallantide than placebo (67 vs 165 minutes), sustained through 24 hours post-treatment, and sustained when administered to patients in episodes 2 to 6.

Severity of adverse events was similar in the ecallantide and placebo groups and was mild or moderate. Seven patients (10%) reported mild, transient injection-site reactions (typically erythema and pruritis). One patient experienced a treatment-related serious adverse event: an anaphylactic/anaphylactoid reaction.

Dr. Levy said she is hopeful and optimistic about ecallantide since there is no approved disease-specific therapy for HAE.

Funding for this study was provided by Dyax.


[Presentation title: Sub-Cutaneous Injection of a Kallikrein Inhibitor Improves Attacks of Hereditary Angioedema. Abstract 398A]

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