CSL Behring announced
today that it has reached the primary endpoint of a Phase III clinical
trial of human pasteurized C1-inhibitor (C1-INH) concentrate to treat
patients with hereditary angioedema (HAE), a rare genetic disorder that can
lead to painful and sometimes life-threatening attacks of edema (swelling)
of the face, airway, abdomen, and extremities.
The results from the Phase III, double blind, placebo-controlled trial
I.M.P.A.C.T. (International Multi-centre Prospective Angioedema
C1-inhibitor Trial), showed that patients treated with 20 U/kg b.w. C1-INH
experienced a highly significant reduction in time to onset of relief of
symptoms of HAE attacks compared to placebo (p= 0.003, one sided). In
addition, all secondary endpoints of the trial have shown significant
positive results, e.g. worsening of symptoms (p= 0.001, one sided).
"The results of this trial can immediately impact the lives of the
thousands of HAE patients around the world who live with the burden of
acute HAE attacks without approved treatment," said Timothy Craig, M.D.,
professor of medicine and pediatrics, Penn State Hershey Medical Center,
USA, coordinating investigator of the I.M.P.A.C.T. trial.
I.M.P.A.C.T. is a multi-center, prospective clinical trial conducted
globally in more than 45 centers in 15 countries, enrolling 125 patients,
and is the largest trial ever conducted in HAE. For the first time, a dose
comparison study was conducted for a human C1-INH comparing 20U/ kg b.w.
and 10U/ kg b.w. in a randomized, placebo-controlled, double-blind study
design. The results will be submitted in the near future to the United
States Food and Drug Administration, Health Canada and European Health
Authorities in support of applications to license C1-INH concentrate for
the treatment of acute attacks of HAE in the U.S., Canada, and Europe. CSL
Behring has manufactured and provided C1-INH concentrate to HAE patients
for over 20 years in Germany, Austria, Switzerland, and several other
countries, where it is licensed under the trade name Berinert(R) P for the
treatment of acute HAE attacks.
"The successful completion of this trial confirms longstanding
observations made from the administration of more than 300,000 treatments
of C1-INH concentrate in Europe. We are delighted that it will now be
submitted for registration in the UK," said Dr. Hilary Longhurst,
Consultant Immunologist, Barts and The London NHS Trust, London, England,
and investigator of the I.M.P.A.C.T. trial.
Study design and results
HAE is caused by the partial absence of functional C1 inhibitor in the
blood. The objective of I.M.P.A.C.T. was to assess whether replacing the C1
protein missing in patients with HAE through treatment with C1-INH can
address the underlying mechanism of the disease.
I.M.P.A.C.T. evaluated in a prospective and double-blind fashion
whether different doses of human pasteurized C1-INH concentrate lead to
faster relief of acute symptoms of abdominal and facial attacks compared
with placebo in patients with HAE. It is also the largest dose comparison
study ever done in HAE. To be eligible for inclusion in the study, patients
had to be six years of age or older, with a diagnosis of C1-INH deficiency
and a documented history of facial or abdominal attacks.
The primary objective was to show that C1-INH shortens the time to
onset of relief of symptoms of abdominal or facial HAE attacks. The primary
endpoint was time between start of C1-INH administration and onset of
relief of symptoms from abdominal or facial attacks as determined by the
subject's assessment. The median time to onset of relief of symptoms in the
20 U/kg b.w. C1-INH treatment group was 30 minutes, compared to 1.5 hours
for patients who received placebo.
The secondary endpoint, that is, the proportion of subjects with
increased intensity of clinical HAE symptoms between two and four hours
after start of study drug administration compared to baseline, showed also
significant improvement (p= 0.001, one sided), as did time to the complete
resolution of HAE symptoms (p= 0.024, one sided). Dose comparison revealed
that the 20 Units C1-INH/kg was significant versus placebo. The 10 Units
C1-INH/kg was superior to placebo, but was not significant.
"C1-INH really made a difference in improving the quality of my life
and that of many other HAE patients," said Henrik Boysen, chairman of the
Patient Association for HAE in Denmark.
"We are excited that the track is set to make this product available in
many countries where currently no licensed product is available."
For more information about HAE, visit allabouthae.
About CSL Behring
CSL Behring is a global leader in the plasma protein biotherapeutics
industry. Passionate about improving the quality of patients' lives, CSL
Behring manufactures and markets a range of safe and effective
plasma-derived and recombinant products and related services. The company's
therapies are used in the treatment of immune deficiency disorders,
hemophilia, von Willebrand disease, other bleeding disorders and inherited
emphysema. Other products are used for the prevention of hemolytic diseases
in the newborn, in cardiac surgery, organ transplantation and in the
treatment of burns. The company also operates one of the world's largest
plasma collection networks, ZLB Plasma. CSL Behring is a subsidiary of CSL
Limited, a biopharmaceutical company with headquarters in Melbourne,
Australia. For more information, visit cslbehring.
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