ViroPharma presents data on Cinryze C1 esterase inhibitor for HAE at ACAAI Meeting

Nov 16 2010

ViroPharma Incorporated (Nasdaq: VPHM) today announced data in four poster presentations and two oral presentations relating to Cinryze® (C1 esterase inhibitor [human]) at the 2010 Annual Meeting of the American College of Allergy, Asthma & Immunology (ACAAI), November 11 through 16 in Phoenix, Ariz.  

Cinryze is the first and only FDA-approved C1 esterase inhibitor therapy indicated for routine prophylaxis against angioedema attacks in adolescent and adult patients with hereditary angioedema (HAE), a rare, debilitating and potentially fatal disease. Cinryze is not approved by the FDA to treat acute angioedema attacks, nor has the safety and effectiveness of Cinryze been established in pediatric patients with HAE.  Cinryze should be used in pregnant women only if clearly needed.

"As awareness and usage of Cinryze to prevent attacks of HAE evolves, it is important that we continually examine and expand the body of scientific data for this important therapy," said Colin Broom, ViroPharma's chief scientific officer.  "Our goal remains to help people suffering from HAE who want to help gain control of their attacks through prophylaxis with Cinryze, rather than relying on treatment of attacks after they have occurred, and to improve the level of education and awareness amongst physicians who may diagnose or manage these patients."

Oral Presentations

In an oral presentation entitled, 'Open-Label Use of Nanofiltered C1 Esterase Inhibitor (human) (Cinryze®) for Treatment or Prophylaxis of Acute Attacks of Hereditary Angioedema (HAE) in Pregnant Subjects,' Dr. James Baker, M.D., of Allergy, Asthma, and Dermatology Associates in Lake Oswego, Ore. discussed the experience of 14 pregnant women who were enrolled in pivotal and open label studies of Cinryze.  In this limited sample, Cinryze was utilized for the therapy of acute attacks and as routine prophylaxis of HAE during pregnancy and delivery.  The study included the following data from 10 pregnant subjects enrolled in the open label prophylaxis study who received a median of 34 doses of Cinryze:

• HAE attack rates for women with pre- and post-pregnancy data improved when using Cinryze for prophylaxis (mean 0.25 attacks per month compared to a pre-Cinryze historical mean monthly attack rate of 4.25 attacks per month;>
• Seven subjects delivered eight healthy neonates including one set of twins; one subject with a history of miscarriage and ectopic pregnancy had a spontaneous abortion, possibly as a result of an ectopic pregnancy; one subject who received her first exposure to Cinryze during the third trimester delivered a stillborn neonate with multiple congenital anomalies; and one outcome was unknown;
• The most common reported adverse events during treatment in open label trials with pregnant subjects were infection, gastrointestinal disorders, and headache; no serious adverse events were considered related to Cinryze;
• There was no evidence of clinically relevant anti-C1-INH antibodies;
• There was no evidence of viral transmission.

In an oral presentation entitled, 'Open Label Use of Nanofiltered C1 Esterase Inhibitor (human) (Cinryze®) for the Treatment of Hereditary Angioedema (HAE) Attacks,' Dr. Marc Riedl, M.D. of the University of California, Los Angeles, David Geffen School of Medicine discussed open label data describing the results of Cinryze in treating 609 attacks of HAE in 101 subjects with HAE.  Forty-three (43) subjects completed the study; most of those discontinuing the study did so because they transferred to the open label prophylaxis study or commercial Cinryze, or 3-month follow up was no longer required.  Data from the study included the following:

• Unequivocal relief, defined as the presence of three consecutive 15 minute assessments consistent with improvement, occurred in 68 percent of attacks within one hour, and 87 percent within four hours;
• Clinical relief, defined as unequivocal relief or the presence of one or two consecutive 15 minute assessments consistent with improvement immediately prior to discharge, occurred in 73 percent of attacks within one hour, and 96 percent within four hours;
• 65 percent of laryngeal attacks achieved unequivocal relief or at least one report consistent with improvement immediately prior to discharge within one hour, and 90 percent within four hours;
• Of the 78 laryngeal attacks, none required intubation after the receipt of Cinryze;
• Responses to Cinryze in subjects with more than one attack did not diminish with subsequent repeated administration;
• Infusion site pain, joint swelling, rash, and sinusitis were reported as treatment-emergent Cinryze-related adverse events.  No treatment-emergent serious adverse events were considered related to study drug.

Poster Presentations

In a poster entitled, 'Open-Label Use of Nanofiltered C1 Esterase Inhibitor (Human) (Cinryze®) for the Prophylaxis of Hereditary Angioedema (HAE) Attacks,' Dr. Ira Kalfus, of M2G Consulting presented open label data describing the efficacy profile of Cinryze in preventing attacks of HAE in 146 adolescent and adult subjects with HAE.  Data from this study included the following:

• Cinryze prophylaxis decreased the median angioedema attack rate from 3.0 to 0.2 attacks per month;
• In subjects treated with Cinryze prophylaxis for more than one year, the degree of protection from HAE attacks was maintained over time;
• With repeat administration of Cinryze, increases in antigenic and functional levels of C1 inhibitor (C1-INH) post therapy were maintained indicating no change in systemic exposure with repeated administration;
• No anti-C1-INH antibodies were detected during this study;
• No subjects were discontinued from Cinryze therapy due to an adverse event.  Headache, nausea, rash erythema and diarrhea were the most frequently reported treatment-emergent Cinryze-related adverse events.

In a poster entitled, 'Open-Label Use of Nanofiltered C1 Esterase Inhibitor (human) (Cinryze®) for the Prophylaxis of Attacks of Hereditary Angioedema (HAE) in Pediatric Subjects,' Dr. David Hurewitz, M.D., Allergy Clinic of Tulsa, Ok., described new open label results of Cinryze in preventing HAE attacks in 23 children with HAE.  Data from this study included the following:

• Cinryze reduced the frequency of HAE attacks from 3.0 attacks per month at baseline to 0.39 attacks per month during Cinryze prophylaxis;
• In children, prophylactic doses of 1000 U of Cinryze every 3 to 7 days resulted in increases in antigenic and functional C1-INH levels comparable to those seen in adults; increases in functional C1-INH activity were maintained over time;
• There were no severe hypersensitivity reactions related to Cinryze; no discontinuations from study due to adverse events; no detectable anti-C1 INH antibodies; and no evidence of transmission of HBV, HCV, or HIV;
• Adverse events considered to be possibly, probably, or definitely related to Cinryze were headache, nausea, and infusion site erythema, none of which were considered severe.

In a poster entitled, 'Open-Label Use of Nanofiltered C1 Esterase Inhibitor (Human) (Cinryze®) for Treatment of Acute Attacks of Hereditary Angioedema (HAE) in Pediatric Subjects,' Dr. William Lumry, M.D., of the University of Texas Southwestern Medical School in Dallas, Texas presented open label experience with Cinryze in treating 121 HAE attacks in 22 pediatric patients. Data from this study included the following:

• The overall median time to beginning of relief of all attacks was 15 minutes;
• Overall response rates within 4 hours were 89 to 97 percent for unequivocal relief and clinical relief, respectively;
• No subjects with a laryngeal attack required intubation;
• In subjects who were treated for multiple attacks, repeated therapy with Cinryze did not diminish the response to treatment;
• Of the 121 acute attacks treated with Cinryze, 88 attacks were treated with one dose of Cinryze; 33 attacks required two doses;
• There were no serious adverse events, and no adverse events were considered related to Cinryze.  No subject discontinued study drug due to an adverse event;  
• There was no evidence of transmission of HBV, HCV, or HIV, and no clinically relevant anti-C1 inhibitor antibodies developed.

In a poster entitled, 'Site of Care of Nanofiltered C1 Esterase Inhibitor [human] (Cinryze®) in Patients with Hereditary Angioedema (HAE),' Ladonna Landmesser, Pharm.D. of ViroPharma Incorporated, presented data describing the use of an internal database of HAE patients and demographic data, as reported by 516 patients as of June 2010, to determine the site of care (SOC) of Cinryze therapy in the U.S. Data from this study included the following:

• 47 percent of patients in this study had Cinryze administered in their homes;
• 28 percent of patients self administered or had members of their family administer the therapy;
• Males and females reported similar results for site of care, except more males received therapy from a family member;
• Patients between the ages of 30 to 44 reported the highest percentage of self administration (24.6 percent);
• Patients over 65 years of age were the largest group to receive Cinryze at physicians' offices (40 percent) and by home health agencies (24 percent).