The FDA ( Food and Drug Administration ) 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.

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 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 hereditary angioedema attacks. By inhibiting the effects of bradykinin, which is thought to be responsible for HAE symptoms of localized swelling, inflammation, and pain, Icatibant 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.

Hereditary angioedema is a rare genetic disease caused by low levels or a dysfunction of C1 esterase inhibitor ( C1-INH ). Reduced C1-INH activity can lead to elevated plasma levels of bradykinin, which is thought to be responsible for HAE symptoms.
Hereditary angioedema is characterized by recurrent sudden attacks of edema of the skin ( hands, arms, feet, legs, thighs, face, genitals ) or the mucous membranes ( gastrointestinal tract, larynx or voicebox ).
The swelling can be disfiguring and painful, especially in case of abdominal attacks. Laryngeal attacks are potentially life-threatening due to the risk of suffocation.
Unlike angioedema caused by allergic reactions, signs and symptoms such as hives and itching do not occur in hereditary angioedema. Signs and symptoms of HAE do not respond to standard treatments for allergic angioedema such as Epinephrine, corticosteroids, and antihistamines.

The efficacy and safety of Firazyr 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 Firazyr ( n=43 ) compared to placebo ( n=45 ) was 2 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 Firazyr and placebo, respectively. Additional rescue medications were used by 3 patients ( 7% ) treated with Firazyr and 18 patients ( 40% ) treated with placebo.

FAST 1 and 2 included a total of 61 Icatibant-treated patients. Across the three controlled trials, Firazyr 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.

Source: Shire, 2011

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