How does Berinert work for Hereditary Angioedema (HAE)?

• Berinert is a man-made form of a protein called C1 esterase inhibitor (C1-INH), that naturally occurs in our blood.
• Berinert is injected intravenously (into a vein) to treat acute abdominal, facial, or laryngeal attacks of hereditary angioedema (HAE) in adults and children.
• People with HAE have reduced levels of C1-INH in their blood, which leads to increased blood vessel permeability and attacks of severe swelling in the limbs, face, intestinal tract, and airway (these attacks of swelling are called angioedema).
• Berinert replaces missing C1-INH, preventing the generation of bradykinin and other substances that increase the permeability of blood vessels.
• Berinert is the only C1-INH that is approved for self-administration for acute abdominal, facial, or laryngeal attacks of hereditary angioedema (HAE) in adults and children. It may also be administered by caregivers or health professionals.

Berinert is a brand of complement C1 esterase inhibitor (C1-INH). C1-INH is a man-made form of a protein in blood that helps control swelling in the body and is used to treat people with a condition called hereditary angioedema who lack C1-INH.

Hereditary angioedema is a genetic disorder that causes attacks of severe swelling in the limbs, face, intestinal tract, and airway.

What is Berinert?

Berinert is a man-made form of the C1-INH. The main purpose of C1-INH is to regulate the coagulation pathway (the process that causes our blood to clot), the fibrinolytic system (the process that removes and degrades clots after blood vessels are repaired), and to control the production of bradykinin, which is a protein fragment that increases the movement of fluid through blood vessel walls, resulting in swelling and inflammation.

How does Berinert work?

People with hereditary angioedema (HAE) have low levels of naturally occurring C1-INH in their blood. During an attack, these levels of C1-INH become so low that angioedema (severe swelling in the limbs, face, intestinal tract, and airway) occurs.

Berinert adds working C1-INH, which brings levels of C1 back up and closer to normal, reducing bradykinin production, decreasing the permeability of blood vessels, and reducing swelling. Berinert is used to treat attacks of angioedema in people with HAE.

How is Berinert given?

Berinert is given by intravenous infusion (slowly into the vein), as soon as possible in people experiencing an acute attack of HAE. It can either be given by a trained nurse or doctor or people (or their caregivers) can be taught how to self-administer it themselves.

95% of Berinert infusions are self-administered at home or in other non-health care settings. An infusion takes about 7 or 8 minutes to self-administer.

Berinert is usually given at a dose of 20 units per kg body weight. It is provided as a freeze-dried powder which needs to be reconstituted.

Are there any other types of C1 inhibitors?

Yes, there are three other types of C1 inhibitors:

• Ruconest is injected intravenously to treat angioedema attacks in adults and adolescents with HAE
• Cinryze, which is injected intravenously every three to four days to prevent angioedema attacks in adults and adolescents with HAE
• Haegarda is injected subcutaneously (under the skin) to prevent angioedema attacks in adults and adolescents with HAE.

What is hereditary angioedema?

Hereditary angioedema is a genetic disorder characterized by severe swelling in the limbs, face, intestinal tract, and airway. There are three known types: Type I and II caused by mutations in the Serping I gene and Type III which is caused by mutations in the F12 gene.

The Serping I gene provides instructions for making the C1 inhibitor protein, which helps control inflammation. Mutations in this gene can lead to either reduced levels of C1 protein in the blood or the production of a C1 inhibitor that functions abnormally. When levels of this C1 protein are decreased, excessive amounts of another protein fragment, called bradykinin are generated. Bradykinin increases the leakage of fluid through the walls of blood vessels into body tissues, promoting inflammation. This causes fluid to accumulate which causes the swelling characteristic of hereditary angioedema type I and type II.

Some cases of hereditary angioedema type III are associated with mutations in the F12 gene. This gene codes for an important protein that helps our blood to clot, known as coagulation factor XII. Factor XII is also an important stimulator of inflammation and is involved in bradykinin production. Certain F12 mutations produce Factor XII with an increased activity, which generates more bradykinin, leading to blood vessel wall leakage and angioedema. The gene mutations responsible for other types of hereditary angioedema III have not yet been discovered.

How effective is Berinert?

A study that treated patients having an acute attack of HAE with Berinert 20 units/kg body weight reported:

• 70.6% of people experienced relief of abdominal symptoms within four hours of the start of treatment compared to 45.5% of people administered a placebo (pretend injection)
• 97.1% experienced a reduction in the severity of symptoms within four hours compared with 87.9% of those administered placebo
• 66.7% of people experienced relief of facial symptoms within four hours of the start of treatment compared to 37.5% of people administered a placebo (pretend injection)
• 66.7% experienced a reduction in the severity of symptoms within four hours compared with 50% of those administered placebo
• Serial facial photos showed severity reduction in facial swelling in 77.8% of those administered Berinert compared to 25% administered placebo
• Only 26% of people administered Berinert needed rescue medication compared with 51.5% of those administered placebo
• Nobody administered Berinert reported worsening of symptoms at 4 hours after administration of study medication compared to baseline
• Berinert 20 unit/kg body weight dose was significantly more effective than the Berinert 10 unit/kg body weight.