The Food and Drug Administration ( FDA ) has granted marketing approval for Firazyr ( Icatibant injection ) for treatment of acute attacks of hereditary angioedema ( HAE ) in adults 18 years of age and older.

Hereditary angioedema is a debilitating rare genetic disease characterized by recurrent, sometimes disfiguring and often painful episodes of acute swelling which can be life-threatening in some cases. The swelling attacks can affect any part of the body but most commonly occur in the face, gastrointestinal tract, extremities or genitals. Laryngeal attacks can be fatal due to the risk of suffocation.

Firazyr has orphan drug designation status in the EU and US for the treatment of acute hereditary angioedema. Firazyr is supplied in a pre-filled syringe that can be stored at room temperature, making it portable and accessible for immediate treatment of hereditary angioedema attacks.
Firazyr's active substance, Icatibant, is a potent and selective bradykinin B2 receptor antagonist. It represents a novel, targeted, subcutaneously administered approach to the treatment of HAE attacks. By inhibiting the effects of bradykinin, which is thought to be responsible for hereditary angioedema symptoms of localized swelling, inflammation, and pain, Firazyr treats the clinical symptoms of an acute hereditary angioedema attack.

After injection training, patients may self-administer Firazyr. Most patients respond to a single dose of Firazyr. If response is inadequate or if symptoms recur, up to 2 additional doses may be administered within a 24 hour period at intervals of at least 6 hours.

The efficacy and safety of Icatibant for the treatment of acute attacks of hereditary angioedema in adults were studied in three double-blind, randomized, controlled clinical trials known as FAST 1, 2 and 3. Among the 223 patients in these studies, the mean age was 38 years, 64% were female, and 95% were white. Approximately 57% of patients reported use of attenuated androgens, antifibrinolytic agents, or C1 inhibitors.

FAST 3 was a placebo-controlled study of 98 adult patients with a median age of 36 years. The primary endpoint was assessed using a 3-item composite visual analog score ( VAS ), comprised of averaged assessments of skin swelling, skin pain, and abdominal pain. The median time to 50% reduction in symptoms for patients with cutaneous or abdominal attacks treated with Icatibant ( n=43 ) compared to placebo ( n=45 ) was 2.0 hours versus 19.8 hours, respectively ( p<0.001 ). The median times to almost complete symptom relief were 8.0 versus 36.0 hours for Icatibant and placebo, respectively. Additional rescue medications were used by 3 patients ( 7% ) treated with Icatibant and 18 patients ( 40% ) treated with placebo.

FAST 1 and 2 included a total of 61 Icatibant-treated patients. Across the three controlled trials, Icatibant had a median time to 50% reduction from baseline symptoms ranging from 2.0 to 2.3 hours.

In an assessment of the first 5 Icatibant-treated attacks ( 621 doses for 582 attacks ), the median times to a 50% reduction from the pretreatment composite 3-itemVAS score were similar across attacks ( 2.0, 2.0, 2.4, 2.0, 1.5 hours ). The majority ( 93% ) of these attacks were treated with a single dose of Firazyr.

Among 60 patients with laryngeal attacks who were treated with Firazyr, efficacy results were similar to those observed for non-laryngeal sites of attack.

Self-administration of Firazyr by 56 patients was assessed in an open label trial. Patients who administered Firazyr during an acute attack of hereditary angioedema had a median time to 50% reduction from the pretreatment composite 3-item VAS score of 2.6 hours. The safety profile in these patients was similar to that of patients whose therapy was administered by healthcare professionals.

Because laryngeal attacks may be fatal, patients with laryngeal symptoms should administer Firazyr and immediately seek medical attention.
The most commonly reported adverse reactions were injection site reactions, which occurred in almost all patients ( 97% ) in clinical trials. These most frequently included redness and swelling.
Other common adverse reactions reported in at least 1% of patients included fever, transaminase increase, dizziness, and rash.

Source: Shire, 2011

XagenaMedicine2011


Link: Xapedia - Medical Encyclopedia