Efficacy and safety of ecallantide in treatment of recurrent attacks of hereditary angioedema: Open-label continuation study

Abstract

Hereditary angioedema (HAE) is a rare disorder characterized by recurrent attacks of potentially life-threatening edema. The plasma kallikrein inhibitor ecallantide is approved for treatment of acute HAE attacks. This study evaluates the efficacy and safety of ecallantide for treatment of multiple HAE episodes in the DX-88/19 (continuation) study. Patients received 30 mg of subcutaneous ecallantide for acute HAE attack symptoms, with no limit on number of episodes treated. Primary end point was change in patient-reported mean symptom complex severity (MSCS) score at 4 hours. Additional end points included change in MSCS score at 24 hours, treatment outcome score (TOS) at 4 and 24 hours, and time to response. Safety parameters included adverse events. Statistical analyses were conducted on qualifying treatment episodes (those with ≥12 patients). One hundred forty-seven patients received treatment for 625 episodes; analyses were conducted through 13 treatment episodes. Across 13 episodes at 4 hours, mean change in MSCS score ranged from -1.04 to -1.36, and mean TOSs ranged from 56.2 to 79.8. Median time to onset of sustained improvement ranged from 59 to 113 minutes. There was no indication of reduced efficacy with repeated ecallantide use. No new safety signals were detected. Eight patients (5.4%) reported potential hypersensitivity reactions, six of whom met the definition of anaphylaxis based on National Institute of Allergy and Infectious Diseases criteria. Ecallantide is effective for acute recurrent HAE attacks and maintains its efficacy and safety during multiple treatment episodes in patients with HAE. Potential hypersensitivity reactions were consistent with prior reports.

Icatibant for Multiple Hereditary Angioedema Attacks across the Controlled and Open-Label Extension Phases of FAST-3

“…The median times to onset of primary symptom relief and almost complete symptom relief were 1.0-2.0 h and 4.8-55.0 h, respectively, for the first to tenth cutaneous and/or abdominal attacks in the OLE phase of FAST-1, and 1.3-3.9 h and 6.5-33.1 h for the first to fifth cutaneous and/or abdominal attacks in the controlled and OLE phases of FAST-2 [9,10]. Similarly, consistency of response over the repeated treatment of multiple attacks has also been reported with other HAE medications, including the kallikrein inhibitor ecallantide [15] and C1-esterase inhibitors [16,17]. However, meaningful comparisons of specific outcomes with different medications are precluded by variations in study designs and efficacy assessments and a lack of head-to-head studies.…”

Ecallantide for the Acute Treatment of Angiotensin-Converting Enzyme Inhibitor–Induced Angioedema: A Multicenter, Randomized, Controlled Trial

“…There were no new safety signals identified, and safety data were consistent with those of previous studies of ecallantide. 26,27 The treatment-emergent adverse events experienced with all treatments were similar in type, distribution, frequency, and severity, although there was a trend toward an increased incidence of such events in the ecallantide treatment group (particularly in the 60-mg dose). The majority of treatmentemergent adverse events were considered not to be drug related.…”

Hereditary and acquired C1-inhibitor-dependent angioedema: from pathophysiology to treatment

“…Ecallantide non-significantly improved the time to improvement of symptoms from 240 min in the placebo group to 165 min in the treatment arm (98). An open-label follow-up study indicates that Ecallantide may indeed shorten the duration of an attack, however, 5% of the patients experienced hypersensitivity reactions (99). As a selective BKR2 antagonist, Icatibant inhibits BK induced vasodilatation in vivo (Figure 4) (17,100).…”