General Information

Ruconest is a recombinant C1 esterase inhibitor. HAE attacks stem from a deficiency of the C1 inhibitor protein in the blood.

Ruconest is specifically indicated for the treatment of acute angioedema attacks in adult and adolescent patients with hereditary angioedema.

Ruconest is supplied as a solution for intravenous use after reconstitution only. The recommended dose of Ruconest is 50 IU per kg with a maximum of 4200 IU to be administered as a slow intravenous injection over approximately 5 minutes. If the attack symptoms persist, an additional (second) dose can be administered at the recommended dose level. Do not exceed 4200 IU per dose. No more than two doses should be administered within a 24 hour period.

Clinical Results

The FDA approval of Ruconest was based on a randomized, double-blind, placebo-controlled, phase III trial (RCT) which included an open-label extension (OLE) phase and is supported by the results of two additional RCTs and two additional OLE studies. The pivotal RCT and OLE studies analyzed the results from 44 subjects who experienced 170 HAE attacks. The primary efficacy endpoint was the time to beginning of symptom relief, assessed using patient-reported responses to two questions about the change in overall severity of their HAE attack symptoms after the start of treatment. These were assessed at regular time points for each of the affected anatomical locations for up to 24 hours. To achieve the primary endpoint, a patient had to have a positive response to both questions along with persistence of improvement at the next assessment time (i.e., the same or better response). A statistically significant difference in the time to beginning of symptom relief was observed in the intent-to-treat population (n=75) between Ruconest and placebo (p=0.031, log-rank test); the median time to beginning of symptom relief was 90 minutes for Ruconest patients (n=44) and 152 minutes for placebo patients (n=31).

Mechanism of Action

Ruconest is a recombinant C1 esterase inhibitor. C1 esterase inhibitor (C1INH) is a normal constituent of human blood and is one of the serine protease inhibitors (serpins). The primary function of C1INH is to regulate the activation of the complement and contact system pathways. Regulation of these systems is performed through the formation of complexes between the protease and the inhibitor, resulting in inactivation of both and consumption of the C1INH. C1INH exerts its inhibitory effect by irreversibly binding several proteases (target proteases) of the contact and complement systems. The effect of Ruconest on the following target proteases was assessed in vitro: activated C1s, kallikrein, factor XIIa and factor XIa. Inhibition kinetics were found to be comparable with those observed for plasma-derived human C1INH.