The treatment was approved for acute HAE attacks in adults and adolescents by the European Medicines Agency (EMA) in 2010, followed by the U.S. Food and Drug Administration (FDA) in 2014. Its safety and efficacy is not well-documented in children.
The study, “Recombinant Human C1 Esterase Inhibitor Treatment for Hereditary Angioedema Attacks in Children,” was published in Pediatric Allergy and Immunology.
Hereditary angioedema, a rare disorder, is characterized by sudden and recurrent episodes of swelling in the face, tongue, hands, feet, gastrointestinal tract, genitalia, and upper airways.
It is caused by a lack of properly working C1-inhibitor (C1-INH) protein, resulting in the continuous production of an enzyme called kallikrein, which, in turn, raises the levels of bradykinin, a peptide that regulates blood pressure and inflammation by dilating blood vessels. Bouts of swelling during HAE attacks are linked to the excessive amounts of bradykinin.
Ruconest, by Pharming, is a recombinant human C1-INH (rhC1-INH) that works by replacing the C1-INH protein missing in HAE patients, relieving the symptoms of acute swelling attacks triggered by the lack of C1-INH in the blood.
An open-label, Phase 2 clinical trial (NCT01359969) evaluated the safety and efficacy of Ruconest, administered intravenously at a dose of 50 U/kg, in controlling acute HAE attacks in children up to 14 years old.
The trial’s primary goal (endpoint) was the time from the attack to the beginning of symptom relief (TOSR), defined as the time interval during which patients reported a decrease of at least 20 mm (relative to a starting measure) on the visual analog scale (VAS), a measure of pain intensity (intense pain is 100 mm).
Secondary endpoints included the time to minimal symptoms (TTMS), defined as the time interval during which patients reported a VAS drop to below 20 mm in all places affected by the attack. This reporting marked clinical remission.
The trial enrolled 20 children, ages 5 through 13, who were treated with Ruconest for a total of 73 HAE acute attacks. More than one third (35.0% or seven children) received treatment for four or more acute attacks.
Results showed that a single dose of Ruconest was sufficient to stop 95.9% of the attacks. The median TOSR was 60.0 minutes, while the median TTMS was 122.5 minutes. Both values were consistent across all attacks.
Ruconest was generally safe and well-tolerated by pediatric patients. The most common adverse events reported in the study included cold (15.0%), vomiting (15.0%), abnormal white blood cells morphology (10.0%) and viral infection (10.0%).
No serious side effects or hypersensitivity reactions to Ruconest were reported. Likewise, none of the children discontinued treatment due to adverse events.
“More than 95% of HAE attacks required only a single dose of rhC1-INH and, overall, findings in children align with published data for adults, indicating that rhC1-INH for HAE attacks is efficacious and well tolerated across various age groups and attack locations,” the researchers wrote.