Home » Drug Information » FDA Approved Drugs » 2009
Medical Areas: Immunology | Pediatrics/Neonatology | Genetic Disease
View By:YearCompanyConditionsTherapeutic AreasDrug Names
Berinert (C1 Esterase Inhibitor (Human))
The following drug information is obtained from various newswires, published
medical journal articles, and medical conference presentations.
Company: CSL Behring
Approval Status: Approved October 2009
Treatment Area: abdominal or facial attacks of hereditary angioedema
Berinet is a human plasma derived, purified, pasteurized, lyophilized concentrate of the protein C1 esterase inhibitor. HAE is caused by the poor functioning of C1 that is present in the plasma and helps control inflammation (swelling) and parts of the immune system.
Berinert is specifically indicated for the treatment of acute abdominal or facial attacks of hereditary angioedema (HAE) in adult and adolescent patients.
Berinert is supplied as a freeze-dried powder for reconstitution for intravenous administration. The recommended initial dose is 20 units per kg body weight by intravenous injection.
The FDA approval of Berinert was based on a placebo-controlled, double-blind, prospective, multinational, randomized, parallel-group, dose-finding, three-arm, clinical study. This study enrolled 124 adult and pediatric subjects with C1 Esterase Inhibitor deficiency who were experiencing an acute moderate to severe attack of abdominal or facial HAE. The subjects were randomized to receive a single 10 unit/kg body weight dose of Berinert, a single 20 unit/kg dose of Berinert or a single dose of placebo by slow intravenous infusion (recommended to be given at a rate of approximately 4 mL per minute) within 5 hours of an attack. If a subject experienced no relief or insufficient relief of symptoms by 4 hours after infusion, investigators had the option to administer a second infusion of Berinert (20 units/kg for the placebo group, 10 units/kg for the 10 units/kg group), or placebo (for the 20 units/kg group). This masked (blinded) rescue study medication was administered to subjects and they were then followed until complete resolution of symptoms was achieved. The objectives were to evaluate whether Berinert shortens the time to onset of relief of
symptoms of an abdominal or facial attack compared to placebo and to compare the efficacy of two different doses of Berinert. Subjects treated with 20 units/kg body weight of Berinert experienced a significant reduction (p≡0.0016) in time to onset of relief from symptoms of an HAE attack as compared to placebo (median of 50 minutes for Berinert 20 units/kg body weight, as compared to >4 hours for placebo). The time to onset of relief from symptoms of an HAE attack for subjects in the 10 unit/kg dose of Berinert was not statistically significantly different from that of subjects in the placebo group. In addition, the efficacy of Berinert 20 units/kg body weight could be confirmed by
observing a reduction in the intensity of single HAE symptoms at an earlier time compared to placebo. Both the proportion of subjects with increased intensity of clinical HAE symptoms between 2 and 4 hours after start of treatment compared to baseline, and the number of vomiting episodes within 4 hours after start of study treatment demonstrated trends in favor of Berinert in comparison to placebo (p values < 0.1). No subjects treated with Berinert at 20 units/kg body weight reported worsening of symptoms
at 4 hours after administration of study medication compared to baseline.
Adverse events associated with the use of Berinert may include, but are not limited to, the following:
- Subsequent HAE attack
- Abdominal pain
- Muscle spasms
Mechanism of Action
Berinet is a human plasma derived, purified, pasteurized, lyophilized concentrate of C1
esterase inhibitor to be reconstituted for intravenous administration. C1 esterase inhibitor is a normal constituent of human plasma and belongs to the group serine protease inhibitors (serpins). C1 esterase inhibitor has an important inhibiting potential on several of the major cascade systems of the human body including the complement system, the intrinsic coagulation (contact) system, the fibrinolytic system, and the coagulation cascade. HAE patients have low levels of endogenous or functional C1 esterase inhibitor. Although the events that induce attacks of angioedema in HAE patients are not well defined, it has been postulated that increased vascular permeability and the clinical manifestation of HAE attacks may be primarily mediated through contact system activation.
Craig TJ, Levy RJ, Wasserman RL, Bewtra AK, Hurewitz D, Obtulowicz K, Reshef A, Ritchie B, Moldovan D, Shirov T, Grivcheva-Panovska V, Kiessling PC, Keinecke HO, Bernstein JA Efficacy of human C1 esterase inhibitor concentrate compared with placebo in acute hereditary angioedema attacks. The Journal of Allergy and Clinical Immunology 2009 Oct;124(4):801-8
De Serres J, Gröner A, Lindner J Safety and efficacy of pasteurized C1 inhibitor concentrate (Berinert P) in hereditary angioedema: a review. Transfusion and Apheresis Science : official Journal of the World Apheresis Association : Official Journal of the European Society for Haemapheresis 2003 Dec;29(3):247-54
Dickneite G Influence of C1-inhibitor on inflammation, edema and shock. Behring Institute Mitteilungen 1993 Dec;(93):299-305
For additional information regarding Berinert or abdominal or facial attacks of hereditary angioedema, please visit the Berinert web page.