Researchers concluded that individual replacement therapy (IRT) with C1-inhibitor (C1-INH) concentrate in patients with severe hereditary angioedema (HAE) significantly reduces the frequency of HAE attacks – especially life-threatening attacks – and significantly improves quality of life, compared to danazol. While attenuated androgens, such as danazol, are the current treatment of choice for prophylaxis of attacks in patients with HAE, these agents can have dangerous side effects, including hypertension, depression, liver adenoma, and in some patients, carcinoma. The data were presented today at the 62nd Annual Meeting of the American Academy of Allergy, Asthma & Immunology (AAAAI).
HAE is a genetic disorder caused by an inherited deficiency of C1-INH. Symptoms include episodes of edema, or swelling, in the hands and feet, the face, the abdomen, and/or the larynx.
"Androgens are standard treatment for HAE, but they do carry the risk of side effects ranging from hypertension, depression, severe headache and virilization to liver adenoma," said Dr. Inmaculada Martinez-Saguer of the Centre of Pediatrics at the J. W. Goethe University Hospital in Frankfurt, Germany, and lead author of the study. "Our findings show that replacement therapy with CI-INH concentrate improves quality of life in patients with frequent and severe HAE attacks. It may be a welcome option for patients in whom attenuated androgens are not tolerated because of severe side effects, or are not effective despite high dosages."
I.M.P.A.C.T. Trial Under Way in North America, Europe
ZLB Behring is currently conducting International Multi-centre Prospective Angioedema C1-inhibitor Trials (I.M.P.A.C.T.), one of which is studying patients with acute abdominal or facial HAE attacks. The purpose of this Phase II/III study, which is being conducted at 45 sites in North America and Europe, is to demonstrate in a prospective and double-blind fashion that human pasteurized C1-INH concentrate leads to faster relief of symptoms of abdominal and facial attacks compared to placebo. The results of this global clinical trial will be submitted to the U.S. Food & Drug Administration (FDA) and Health Canada in support of applications to license C1-INH concentrate for use in North America.
ZLB Behring has manufactured and sold C1-INH concentrate for over 20 years in Germany, Austria, Switzerland, and several other countries in which it is licensed under the trade name Berinert® P for the treatment of acute HAE attacks.
Today's Presentation: Study Design
The prospective, observational, intra-individual, crossover study compared the efficacy, safety and quality of life of danazol (prophylaxis) vs. C1-INH concentrate (IRT) in 23 patients suffering from frequent and severe HAE attacks.
Mean annual attack frequency decreased from 48.8 ± 37.1 (danazol) to 8.1 ± 22.1 (C1-INH); p<0.001. All patients who received pasteurized C1-INH concentrate were free of life-threatening attacks (laryngeal edema) or adverse events, which did occur under long-term prophylaxis with danazol. In addition, all quality of life parameters improved significantly (p<0.001). During the entire 20-year observation period, among the C1-INH concentrate-treated patients there were no transmissions of HIV type 1/2; hepatitis A-, B-, C-, G-viruses; or parvovirus B19.
About Hereditary Angioedema (HAE)
HAE due to C1-INH deficiency is characterized by relapsing, self-limiting episodes of edema at various body sites – mostly subcutaneous tissue, the wall of the intestine, and the larynx. There are estimates of 6,000 to 10,000 or more people with HAE in the United States. Patients who have abdominal attacks experience episodes of severe pain, diarrhea, nausea, and vomiting caused by swelling of the intestinal wall. Attacks that involve the face and throat can result in airway closure, asphyxiation and, if left untreated, death. HAE is caused by a genetic deficiency of C1-INH, which is inherited in an autosomal dominant manner. No FDA-approved product for treatment of acute HAE attacks is available in North America.
About ZLB Behring
ZLB Behring is a global leader in the plasma protein biotherapeutics industry. Dedicated to improving the quality of life for patients throughout the world, ZLB Behring provides safe and effective plasma-derived and recombinant products and offers patients a wide range of related services. The company’s broad portfolio of life-saving therapeutics is used in the treatment of individuals with hemophilia and other bleeding disorders, immune deficiency disorders, and inherited emphysema; for the prevention of hemolytic diseases for the newborn; in cardiac surgery patients; and in shock and burn victims. Additionally, ZLB Behring operates one of the world’s largest, fully owned plasma collection networks. ZLB Behring is a subsidiary of CSL Limited, a biopharmaceutical company, which operates worldwide from its headquarters in Melbourne, Australia. For more information, please visit www.ZLBBehring.com.