EXTON, Pa., Jan. 16, 2013 /PRNewswire/ -- ViroPharma Incorporated (VPHM) today announced the publication of data demonstrating that use of Cinryze (C1 esterase inhibitor [human]) in pediatric patients provided relief from symptoms of hereditary angioedema (HAE) attacks and reduced the rate of attacks. HAE is a rare, severely debilitating, life-threatening genetic disorder caused by a deficiency of a human plasma protein called C1 inhibitor. The paper entitled Nanofiltered C1-Esterase Inhibitor for The Acute Management and Prevention of Hereditary Angioedema Attacks Due to C1-Inhibitor Deficiency in Children by Dr. William Lumry et al. describes the efficacy and the safety profile of Cinryze in prevention and treatment of HAE attacks in the largest analysis of pediatric data from prospective studies of patients with HAE ever reported in medical literature. The article is in press at The Journal of Pediatrics and was posted online on January 14, 2013.
Cinryze is approved by the U.S. Food and Drug Administration (FDA) for routine prophylaxis against angioedema attacks in adolescent and adult patients with HAE; Cinryze is not approved to treat HAE attacks or for procedural prophylaxis. Cinryze is not approved for use in children.
According to published literature, in most patients with HAE, clinical symptoms manifest in childhood, typically between the ages of four and 11 years and may worsen during puberty. Symptoms and frequency of attacks increase during periods of intense physiologic development, such as between the ages of three and 6 years and with onset of puberty. Subcutaneous edema and recurrent abdominal pain caused by gastrointestinal edema are the most common manifestations in children. Common attack triggers include infections, emotional stress, and tissue trauma. Asphyxia is possible when angioedema involves the upper airway and can occur rapidly in children because of narrow airway diameter. Despite this, the diagnosis of HAE is often delayed until late adolescence or adulthood.
Data from the Routine Prophylaxis Placebo-Controlled StudyFour pediatric patients (ages 9 to 17 years) enrolled in and completed the pivotal prophylaxis trial. Children had a nearly 2fold reduction in number of HAE attacks while receiving Cinryze for prophylaxis compared with the time period during which they received placebo (mean number of attacks: 7.0 vs 13.0 over 12 weeks), consistent with the published data from the study population as a whole (6.26 vs. 12.73).
Data from the Open-Label Extension of the Routine Prophylaxis StudyTwenty-three children received open-label Cinryze for routine prophylaxis. Prior to enrollment, the median monthly attack rate was 3.0 and decreased to 0.39 while the patients were receiving Cinryze for routine prophylaxis. The majority of patients (20/23, 87 percent) experienced less than or equal to one attack per month, and 22 percent reported no attacks during the study period.
Pre-procedural ProphylaxisEight children received Cinryze prior to 40 procedures; 90 percent of which were dental procedures. A single 1000 U dose of Cinryze was administered prior to 39 procedures, and two 1000 U doses were administered over a 48-hour period for one procedure per investigator's discretion. Across all procedures, only one HAE attack was reported within 72hours after pre-procedural dosing; no attacks occurred during or within 2 days of the administration of Cinryze.
Data from the Placebo-Controlled Study on Treating HAE AttacksTwelve pediatric patients were treated for an attack (7Cinryze, 5placebo) in the placebo-controlled acute-attack treatment study. Another 3children received open-label Cinryze for treatment of laryngeal angioedema and/or prior to emergency surgical procedures. Unequivocal relief of the defining symptom began within 4 hours after initial treatment in 71 percent of patients (5 of 7) receiving Cinryze, consistent with the rate observed in the study population as a whole (60 percent), compared with 2 of 5 patients receiving placebo. For those children who achieved unequivocal relief, the median time to the beginning of unequivocal relief was 30 minutes with Cinryze compared with 2 hours with placebo.
Data from the Open-Label Study on Treating Acute Attacks In the open-label acute extension, 22 pediatric patients experienced 121 attacks. Eighty-eight attacks were treated with one dose of Cinryze and 33 attacks with two doses. Unequivocal relief started within 1 hour after the initial dose of Cinryze in 79 percent of attacks and within 4 hours after the initial dose in 89 percent of attacks. In the majority of laryngeal attacks, unequivocal relief started within 1 hour, and no child receiving Cinryze required intubation or hospitalization for a laryngeal attack. Response rate within 4hours and time to beginning of relief remained consistent irrespective of attack number or location. In addition, one hundred seventeen attacks were evaluated for clinical relief (discharged to home prior to obtaining all assessments required for unequivocal relief); 113 of 117 (97 percent) achieved clinical relief within 4 hours.
Safety DataIn the pivotal prophylaxis study, one patient experienced pyrexia that was considered by the investigator to be possibly related to study drug. In the open-label prophylaxis extension, 17 of 23 patients reported adverse events; two patients reported a total of three adverse events that were considered by the investigator to be related to Cinryze: One patient had headache and nausea, and the other had infusion-site erythema. All 3 of these events were mild in severity.
No adverse events were reported in the acute-attack treatment trial. In the open-label treatment extension, 9of 24 subjects reported adverse events. No adverse events in the open-label treatment extension were considered by the principal investigator to be related to Cinryze.
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Sub-Group Analysis Of Data From Pediatric Patients With Hereditary Angioedema Published In The Journal Of Pediatrics