EXTON, Pa., Nov. 13, 2012 /PRNewswire/ -- ViroPharma Incorporated (Nasdaq: VPHM) today announced important data from an open-label, multicenter study to assess the safety, tolerability, and treatment effect of escalating doses of C1 INH-nf in patients with HAE who were not adequately controlled with 1000 U every 3 or 4 days. The results of this study were presented at the 2012 annual meeting of the American College of Allergy, Asthma and Immunology (ACAAI) in Anaheim, California. The data provide evidence for the safety profile of Cinryze ® (C1 esterase inhibitor [human]) at doses up to 2500 units in patients with hereditary angioedema (HAE). HAE is a rare, severely debilitating, life-threatening genetic disorder caused by a deficiency of a human plasma protein called C1 inhibitor. The presentation titled, Safety and Efficacy of Escalating Doses of C1 Esterase Inhibitor [Human] (Cinryze) as Prophylaxis in Patients with Hereditary Angioedema (HAE) was presented by Dr. Jonathan A. Bernstein from the University of Cincinnati. The study was a post marketing FDA requirement to assess the safety and tolerability of escalating doses of Cinryze, with specific interest in thrombogenicity and immunogenicity.
This study enrolled 20 eligible subjects over a 3 year period. Subjects with qualifying HAE attack rates, and who met other specified entry criteria, were entered into a 3-step dose-escalation algorithm. Each step consisted of 12 weeks of sequential Cinryze dose escalation of 1500, 2000, and 2500 units with infusions every 3 or 4 days if the subject continued to have an average of >1.0 angioedema attacks/month, regardless of severity. An additional 3 month safety follow-up occurred with successful completion of a dose escalation step. The authors concluded that doses up to 2500 units every 3 or 4 days may be considered for patients who do not respond to 1000 units twice weekly. The results of the study showed that:
- Overall, the safety profile of Cinryze doses up to 2500 units was consistent with previous clinical trial experience at lower doses;
- No systemic thrombotic events occurred during this study;
- At all dosage levels, Cinryze was well tolerated, with no discontinuations due to an adverse event (AE);
- The majority of AEs were mild to moderate intensity;
- During the 12 month study, 2 patients experienced AEs that the investigator considered to be related to study medication (1 with localized blood clot in a port-a-cath on Day 81 treated with streptokinase, catheter-site pain on first day of dosing of two dose escalation steps, and dyspnea on Day 173 and 1 with muscle spasm);
- Two patients experienced serious adverse events unrelated to study medication (one with cerebral cystic lymphangioma and one with worsening anemia and bile duct stone);
- In one patient, C1 INH antibodies were detected at baseline (pre-dose Day 1) and in all samples collected during the study while receiving doses up to 2500 units. Another patient developed borderline detectable antibodies to C1 inhibitor while receiving 2500 units of study drug.
"The study analysis of these data provides insight into the safety and efficacy of dose escalation of Cinryze up to 2500 units," commented Dr. Jonathan A. Bernstein, professor of clinical medicine, Department of Internal Medicine, University of Cincinnati Medical Center, "Previous Cinryze studies show that patients had reductions in the frequency, severity, and duration of angioedema attacks while receiving 1000 units; however, some patients were not adequately controlled at this dose. We are pleased to see that higher doses of Cinryze do not result in systemic thrombotic events, and may be considered for patients with HAE who do not respond to lower doses."
About Cinryze ® (C1 esterase inhibitor [Human])Cinryze is a highly purified, pasteurized and nanofiltered plasma-derived C1 esterase inhibitor product. In the U.S., Cinryze is approved by the FDA for routine prophylaxis against angioedema attacks in adolescent and adult patients with HAE. In the E.U., the product is approved by the EMA for the treatment and pre-procedure prevention of angioedema attacks in adults and adolescents with hereditary angioedema (HAE), and routine prevention of angioedema attacks in adults and adolescents with severe and recurrent attacks of hereditary angioedema (HAE), who are intolerant to or insufficiently protected by oral prevention treatments or patients who are inadequately managed with repeated acute treatment. Cinryze is for intravenous use only.