General Information

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, facial, or laryngeal hereditary angioedema (HAE) attacks in adult and pediatric 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.

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.

Clinical Trial Results

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.