C1-inhibitor (C1-INH) concentrate is effective in safely relieving abdominal pain and abdominal-wall tension in patients with hereditary angioedema (HAE) who experience abdominal attacks, according to data presented today at the American Academy of Allergy, Asthma & Immunology (AAAAI) 62nd Annual Meeting. According to the study, the first to report detailed and quantitative data on treated and untreated attacks of HAE in this large a sample size, in most attacks, relief of these symptoms occurred within 30 to 150 minutes after receiving C1-INH concentrate.
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.
"Our findings are encouraging for the HAE treatment community and patients who experience the extremely distressing symptoms of this very serious disease," said Prof. Dr. Konrad Bork of the Department of Dermatology, Johannes Gutenberg University, Germany, and lead author of the study. "Though in some countries, C1-INH concentrate has been licensed for several years to treat attacks of HAE, the benefits of this product have not been clinically demonstrated in such a large number of patients with abdominal edema. This study adds to the growing body of research on the role of C1-inhibitor concentrate in treating HAE."
I.M.P.A.C.T. Trial Under Way in North America, Europe
No approved treatment for acute HAE attacks is available in North America. 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 acute 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 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
Findings were based on a retrospective clinical analysis of 81 HAE patients. The data included 5,614 severe abdominal attacks treated with C1 inhibitor concentrate versus 18,271 severe untreated abdominal attacks over almost 30 years. The untreated attacks, which occurred before the availability of C1-INH concentrate, were compared with those treated with C1-INH concentrate in the same individuals. Data were generated by asking patients about symptoms they experienced during attacks of HAE; concerns addressed included severity of pain, vomiting, diarrhea, symptoms of hypovolemia, and the course of the attacks. Documentation was performed by standardized questionnaires and scores. Mean time to relief of symptoms was 53.5 minutes when treated early (i.e., within the first 5 hours of the attack), compared with 114 minutes when treatment was delayed. When the injections of C1-INH concentrate were performed correctly, no drug-related adverse events or serious adverse events were observed.
In the study, the mean duration of abdominal attacks until complete relief of all symptoms was 92.0 hours when untreated, compared to 39.9 hours when treated. Patients reported a mean maximal pain score of 8.6 (range, 1-10) for untreated attacks compared to 4.5 when treated.
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.
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.