Fran Lowry

November 25, 2010

November 25, 2010 (Phoenix, Arizona) — Icatibant (Jerini, Berlin, Germany) provides a quick resolution of life-threatening acute laryngeal hereditary angioedema (HAE) attacks, according to a new study presented here at the American College of Allergy, Asthma & Immunology 2010 Annual Scientific Meeting.

The selective bradykinin beta-2 receptor antagonist, which is given subcutaneously for the treatment of HAE, is an investigational therapy in the United States that has not yet been approved by the US Food and Drug Administration, said Marc Riedl, MD, from the University of California at Los Angeles David Geffen School of Medicine.

"Hereditary angioedema is caused by a protein deficiency that leads to acute attacks of abdominal, cutaneous, or laryngeal edema," he told Medscape Medical News. "Laryngeal attacks are the most frightening to both patients and physicians because of their life-threatening nature."

To illustrate his point, Dr. Riedl recounted the following story: "We recently had a regional meeting of HAE patients and I met a gentleman who was the only remaining member of his family who was still alive with HAE. He had lost 3 of his family members in the previous 10 years to laryngeal edema and asphyxiation. So make no mistake — people are still dying from laryngeal attacks of HAE," he said.

One of the family members was the man's sister, who died from her first laryngeal attack. "She was in her mid 20s, she had never had symptoms and had never bothered to get tested, even though HAE ran in the family. Her first attack was a rapidly progressive laryngeal attack, and by the time they got her to emergency [care], she had passed away."

Dr. Riedl presented results from the controlled and open-label extension phases of the For Angioedema Subcutaneous Treatment 1 (FAST-1) trial, which was undertaken to assess the efficacy and safety of icatibant in stopping such reactions.

During the controlled phase, patients with a first laryngeal HAE attack received 1 subcutaneous injection of open-label icatibant 30 mg. During this phase of study, subsequent laryngeal attacks were treated with up to 3 injections (if needed) given 6 hours apart. Repeat dosing was possible if symptoms worsened within 48 hours.

Twenty-six patients experienced a total of 45 laryngeal attacks; 8 of these were in the controlled phase and 37 were in the open-label extension phase of the FAST-1 trial. The majority of the attacks (69%) were assessed as moderate to very severe in intensity.

There was rapid improvement in symptom severity when icatibant was administered. Symptoms became mild or disappeared altogether within 4 hours; these results were obtained in 100% of the attacks in the controlled phase and in 84% of attacks in the open-label phase. The response was irrespective of attack severity, and all symptoms resolved within 24 hours, Dr. Riedl said.

According to the patients, their symptoms regressed after 0.6 hours during the controlled phase, and between 0.3 and 1.2 hours during the open-label phase. According to the investigators, symptoms began to improve after a median of 1 hour, and the time to overall patient improvement was 0.8 hours.

One injection was enough to resolve 86.5% of the attacks. Two injections were needed to stop 10.8% of attacks, and 3 injections were needed to stop 2.7% of attacks.

In addition, 3 attacks required rescue medication during the controlled phase of FAST-1, and 3 required rescue medication during the open-label phase, Dr. Riedl said.

"The use of rescue medication was low, but not 0," he noted. "This is an area where we need additional work to understand more precisely what that rate of rescue really is, particularly when we treat serious attacks like laryngeal edema," he said, adding: "I want to make sure clinicians know that there are those few cases [that require] rescue treatment."

There were no serious drug-related events, although all patients experienced some mild transient injection-site reactions, including swelling, burning, and itching, which resolved within 2 hours, Dr. Riedl said.

After his talk, Dr. Riedl said in an interview with Medscape Medical News that the untimely deaths from laryngeal HAE have taught him that families should get tested for the disease, and referred to the case he described. "That was a great example. She had no symptoms until her 20s, and her first attack was fatal. So testing is important; being prepared is very important. Now that we have medications, fatalities become even more preventable."

He mentioned that a genotyping program is currently ongoing to look for biomarkers that would predict who is at risk for potentially fatal attacks. "We're not there yet, but we hope this work will yield some answers, especially now that we have a way to treat patients," he said.

"This is a very important study. We have never had this agent before; this is something new," said Marianne Frieri, MD, from Nassau University Medical Center, East Meadow, New York, who was one of the moderators of the session. "If we can identify these patients properly, we may be able to prevent an attack and save lives."

Joseph A. Bellanti, MD, professor of pediatrics and microbiology–immunology at Georgetown University Medical Center in Washington, DC, pointed out that the study adds information "that is very valuable, clinically."

The study was sponsored by Jerini (Berlin, Germany). Dr. Riedl reports financial relationships with Jerini/Shire, ViroPharma, Dyax, and CSL Behring. Dr. Frieri and Dr. Bellanti have disclosed no relevant financial relationships.

American College of Allergy, Asthma & Immunology (ACAAI) 2010 Annual Scientific Meeting: Abstract 23. Presented November 14, 2010.


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