Ruconest

What is Ruconest?
The active substance of Ruconest™ (conestat alfa) is a recombinant human C1 esterase inhibitor (rhC1INH). Ruconest is obtained from the milk of rabbits that have been specially bred to have the gene that produces the human C1 inhibitor protein and to produce C1 inhibitor in their milk. rhC1INH (Ruconest) has a high purity, identical amino acid sequence and comparable biological activity to the native protein.  Ruconest is not derived from human plasma why there is no risk of human viral transmission.

What is Ruconest used for?
Ruconest is used to treat acute angioedema attacks in adults with hereditary angioedema (HAE). HAE is a rare disease affecting 1 in 10,000 to 1 in 50,000 persons. It is characterized by recurrent episodes of painful and disabling intense swelling (angioedema), often located to legs and arms or to the abdomen. It is not unusual that the attack is located to the face and sometimes to the mouth and throat which is a life-threatening condition if left untreated. The frequency of attacks range from every 3 days to virtually never but with an average frequency of 8 attacks per year. The cause of the disease is an inherited or acquired genetic defect of the gene encoding the C1 inhibitor protein causing low levels of the functional protein.  A low level or decreased function of C1 inhibitor is thought to be the major reason for recurrent swelling in different parts of the body.  

How does Ruconest work?
Ruconest is a replacement therapy to correct low levels of the C1 inhibitory protein in HAE patients. During an attack, administration of Ruconest will restore functional C1 inhibitor to normal physiological level, reduce the symptoms and stop the attack. The protein is an important regulator by inhibiting a number of proteases in the complement, contact and fibrinolytic systems. Restoring the plasma levels of functional C1 inhibitory will result in homeostatic balance.

How is Ruconest used?
In the event of an attack, the recommended dose of 50 U/kg of Ruconest should be administered by healthcare professional intravenously after reconstituting the Ruconest powder with sterile water for infusion. Patients must be closely monitored and carefully observed for any symptoms of allergic reactions throughout the administration period.

How has Ruconest been studied?
Efficacy, safety and tolerability of Ruconest have been assessed in several phase I, II and III clinical studies including healthy volunteers and both asymptomatic and symptomatic patients with HAE. Time to beginning of relief of symptoms for all anatomical locations (abdominal, genitourinary, facial-laryngeal or peripheral) has been studied. The combined analysis of two independent randomized placebo-controlled trials was reported by Zuraw et al. in Journal of Allergy and Clinical Immunology (October 2010). Efficacy and safety in 70 HAE patients have been evaluated in doses of both 50 and 100 U/Kg of rhC1INH for the treatment of acute angioedema attacks.

What benefits has Ruconest shown?
The randomized controlled studies showed that relative to placebo, both the 50U/kg and 100 U/kg doses of Ruconest were associated with a statistically significant reduction in time to relief of symptoms (median 122 and 66 min respectively, both P < 0.05) and time to minimal symptoms (P < 0.05). Both 50 U/kg and 100 U/kg were considered equally effective in the treatment for acute HAE attacks, providing initial relief of angioedema symptoms in less than 4 hours for 95% of patients, and with no relapses.

What risks are associated with Ruconest?
In safety and tolerability assessments of the studies, Ruconest was proved to be well tolerated up to doses of 100 U/kg.  Across these studies, there were few reports of adverse events and no reports of immune responses or neutralizing antibody activities against either C1INH or to traces of rabbit proteins. Only one reported event of a severe allergic reaction to rhC1INH occurred in a healthy volunteer, who did not disclose a history of rabbit allergy. As with any intravenously administered protein product, hypersensitivity reactions cannot be excluded. Before start of Ruconest treatment the patient must be tested for the presence of IgE antibodies against rabbit dander and show a negative test.

The marketing authorization holder of Ruconest, Pharming Technologies BV, will establish a Ruconest Registry to actively monitor the safety of the use of the product in clinical routine.

Why has Ruconest been approved?
The Committee for Medicinal products for Human Use (CHMP) decided that Ruconest seems to be an effective treatment of acute attacks of HAE. The CHMP decided that Ruconest’s benefits are greater than its risks and recommended that Ruconest be given marketing authorization (October 2010).

Other information about Ruconest
Each HAE patient who tested negative for the presence of IgE antibodies against rabbit dander should be given a Ruconest™ Patient Card to always be carried with them.