General Information

Firazyr (icatibant) is a competitive antagonist selective for the bradykinin B2 receptor. Bradykinin is a vasodilator which is thought to be responsible for the characteristic hereditary angioedema symptoms of localized swelling, inflammation, and pain. Icatibant inhibits bradykinin from binding the B2 receptor and thereby treats the clinical symptoms of an acute, episodic attack of hereditary angioedema.

Firazyr is specifically approved for the treatment of acute attacks of hereditary angioedema in adults.

Firazyr is supplied as a solution for subcutaneous administration. The recommended dose is 30 mg administered by subcutaneous injection in the abdominal area. Additional doses may be administered at intervals of at least six hours if response is inadequate or if symptoms recur. No more than three doses may be administered in any 24 hour period.

Mechanism of Action

Firazyr (icatibant) is a competitive antagonist selective for the bradykinin B2 receptor. Hereditary angioedema is caused by an absence or dysfunction of C1-esterase-inhibitor, a key regulator of the Factor XII/kallikrein proteolytic cascade that leads to bradykinin production. Bradykinin is a vasodilator which is thought to be responsible for the characteristic HAE symptoms of localized swelling, inflammation, and pain. Icatibant inhibits bradykinin from binding the B2 receptor and thereby treats the clinical symptoms of an acute, episodic attack of HAE.

Side Effects

Adverse events associated with the use of Firazyr may include, but are not limited to, the following:

• injection site reactions
• pyrexia
• transaminase increase
• dizziness
• rash

Clinical Results

The FDA approval of Firazyr was based on controlled clinical trials in 223 subjects. Trial 1 was a randomized, placebo-controlled, double-blind, parallel-group study of 98 adults who had developed moderate to severe cutaneous or abdominal or mild to moderate laryngeal attacks of HAE. The subjects were randomized to receive either Firazyr 30 mg or placebo by subcutaneous injection. Subjects with severe laryngeal attacks of HAE received open-label Firazyr 30 mg. The primary endpoint was assessed using a 3-item composite visual analog score (VAS). Response was defined as at least a 50% reduction from the pretreatment composite 3-item VAS score. The median time to 50% reduction in symptoms for subjects treated with Firazyr compared to placebo was 2.0 hours [ersus 19.8 hours, respectively (p<0.001). The median times to almost complete symptom relief were 8.0 versus 36.0 hours for Firazyr and placebo, respectively. In terms of rescue medication use, 3/43 (7%) subjects treated with Firazyr used additional rescue medication in comparison to 18/45 (40%) subjects treated with placebo. In a second placebo-controlled trial and an active-controlled trial, a total of 26 and 35 subjects, respectively, received Firazyr 30 mg for the treatment of an acute HAE attack. Across the three trials, Firazyr had a median time to 50% reduction from baseline symptoms ranging from 2.0 to 2.3 hours.