What is Ruconest used for and how does it work?

• Ruconest is injected intravenously to treat angioedema attacks in adults and adolescents with hereditary angioedema (HAE).
• People with HAE have reduced levels of C1-INH in their blood, which leads to attacks of severe swelling in the limbs, face, intestinal tract, and airway.
• Ruconest treats an acute attack of swelling by replacing missing C1-INH in the blood of people with HAE, decreasing levels of bradykinin, and other substances that increase the permeability of blood vessels, relieving swelling.
• Ruconest may not be as effective at treating facial and laryngeal (around the larynx) attacks compared to abdominal or limb attacks.
• Ruconest is made using recombinant DNA technology. It contains a protein called C1 esterase inhibitor (C1-INH), that naturally occurs in our blood.

Ruconest is a C1 esterase inhibitor (C1-INH) that may be given to treat swelling attacks in adult and adolescent patients with hereditary angioedema (HAE).

Ruconest is made by recombinant DNA technology, using the milk of transgenic rabbits (these are rabbits that have been genetically altered by the transfer of a gene from cows that promotes the production of casein found in milk). This technology means the C1-INH in Ruconest resembles human C1-INH, even though it isn’t derived from humans.

C1-INH naturally occurs in our blood, and it helps 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.

People with HAE lack this C1 protein in their blood or the protein does not work as it should.

Ruconest replaces missing or defective C1-INH, reducing swelling and decreasing blood vessel permeability.

How does Ruconest work?

People with hereditary angioedema (HAE) have low levels of naturally occurring C1-INH in their blood. Ruconest 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.

How is Ruconest given?

Ruconest is given by slow intravenous injection, over approximately 5 minutes. The usual dosage to treat an acute attack of angioedema is 50 units per kg to a maximum of 4200 units.

If attack symptoms persist a second dose can be administered at the same dose level. No more than two doses should be administered within 24 hours.

Ruconest is usually administered by a trained health professional experienced at treating HAE; however, in certain circumstances, some people may be taught how to administer it themselves.

How effective is Ruconest?

The proportion of patients who obtained relief from Ruconest within four hours depending on the different anatomical location of their HAE attack is:

• Abdominal: 88%
• Facial: 50%
• Limbs (arms and legs): 85%.

Are there any other types of C1 inhibitors?

Yes, there are three other types of C1 inhibitors:

• Berinert, which is used to treat attacks of angioedema
• Cinryze, which is given every three to four days by intravenous injection to prevent attacks of angioedema
• Haegada which is given every three to four days by subcutaneous injection to prevent attacks of angioedema.

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.