ViroPharma Incorporated: Cinryze(R) (C1 Esterase Inhibitor [Human]) Data Presented at 2010 International Scientific Conference of the World Allergy Organization (WAO)
This is the first international presentation of these data, which were first presented at the November 2010 Annual Meeting of the American College of Allergy, Asthma & Immunology (ACAAI).
Cinryze is the first and only U.S. 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 currently available only in the United States. Cinryze is not approved by the U.S. 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.
"These scientific posters mark the first international presentation of these important data which highlight the use of Cinryze across a range of patient populations," commented Glenn Tillotson, Ph.D., ViroPharma's head of US medical affairs. "ViroPharma has been acknowledged as the U.S. leader in medical education about hereditary angioedema. However, as we prepare to expand the usage of Cinryze to other parts of the world, it is essential that we broaden our focus, so that physicians around the globe are aware of the severity of disease, and the importance of Cinryze as an essential option for patients who want to gain control of their HAE attacks through prophylaxis, rather than relying purely on acute treatment to terminate their attacks once they have occurred. This World Congress of Allergy Scientific Congress is the first of many such opportunities."
WAO Poster Presentations
In a poster entitled, 'Open-Label Use of Nanofiltered C1 Esterase Inhibitor (Human) (nf-C1 INH) for Treatment or Prophylaxis of Acute Attacks of Hereditary Angioedema (HAE) in Pregnant Subjects,' Dr. Glenn Tillotson Ph.D., FCCP, ViroPharma Incorporated, Exton, PA, presented 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; n=8);
- 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 after the first trimester/organogenesis delivered a stillborn neonate with multiple congenital anomalies; and one outcome was unknown;
- The most commonly reported adverse events during therapy 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 a poster entitled, 'Open-Label Use of Nanofiltered C1 Esterase Inhibitor (Human) (nf-C1 INH for the Prophylaxis of Hereditary Angioedema (HAE) Attacks,' Dr. Steven Villano, M.D., ViroPharma Incorporated, Exton, PA, presented open label data describing the efficacy profile of Cinryze in preventing attacks of HAE in 146 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) (nf-C1 INH) for the Treatment of Hereditary Angioedema (HAE) Attacks,' Dr. Timothy Craig, M.D. of the Hershey Medical Center in Harrisburg, PA, described 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 95 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 84 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.
In a poster entitled, "Open-Label Use of Nanofiltered C1 Esterase Inhibitor (Human) (nf-C1 INH) for Treatment of Acute Attacks of Hereditary Angioedema (HAE) in Pediatric Subjects,' Dr. Timothy Craig, M.D. of the Hershey Medical Center in Harrisburg, PA, presented open label experience with Cinryze in treating 121 HAE attacks in 22 pediatric patients with HAE. 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, 'Open-Label Use of Nanofiltered C1 Esterase Inhibitor (human) (nf-C1 INH) for the Prophylaxis of Attacks of Hereditary Angioedema (HAE) in Pediatric Subjects,' Dr. Colin Broom M.D., ViroPharma Incorporated, Exton, PA, presented new open label results of Cinryze in preventing HAE attacks in 23 pediatric patients with HAE. Data from this study included the following:
- Cinryze reduced the frequency of HAE attacks from a median of 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 addition, the WAO has joined with The American College of Allergy, Asthma and Immunology (ACAAI) and the American Gastroenterological Association (AGA) Institute in an innovative initiative called "HAE: Learn About It, Talk About It." The peer-driven campaign is designed to foster communication between physicians on the front lines of the diagnosis and management of HAE. The addition of WAO as a "Learn About It, Talk About It" partner expands the program to a global audience. The program will be highlighted in booth 13 at the WAO meeting.
About Cinryze® (C1 esterase inhibitor [human])
Cinryze is a highly purified, pasteurized and nanofiltered plasma-derived C1 esterase inhibitor product that has been approved by U.S. FDA for routine prophylaxis against angioedema attacks in adolescent and adult patients with HAE. C1 inhibitor therapy has been used acutely for more than 35 years in Europe to treat patients with C1 inhibitor deficiency.
Severe hypersensitivity reactions to Cinryze may occur. Thrombotic events have occurred in patients receiving Cinryze for routine prophylaxis, and in patients receiving off-label high dose C1 inhibitor therapy. Monitor patients with known risk factors for thrombotic events. With any blood or plasma derived product, there may be a risk of transmission of infectious agents, e.g. viruses and, theoretically, the CJD agent. The risk has been reduced by screening donors for prior exposure to certain virus infections and by manufacturing steps to reduce the risk of viral transmission including pasteurization and nanofiltration. The most common adverse reactions observed have been upper respiratory infection, sinusitis, rash and headache. No drug-related serious adverse events (SAEs) have been observed in clinical trials.
Cinryze is for intravenous use only. A dose of 1000 Units of Cinryze can be administered every 3 or 4 days for routine prophylaxis against angioedema attacks in HAE patients. Cinryze is administered at an injection rate of 1 mL per minute.
About Hereditary Angioedema (HAE)
HAE is a rare, severely debilitating, life-threatening genetic disorder caused by a deficiency of C1 inhibitor, a human plasma protein. This condition is the result of a defect in the gene controlling the synthesis of C1 inhibitor. C1 inhibitor maintains the natural regulation of the contact, complement, and fibrinolytic systems, that when left unregulated, can initiate or perpetuate an attack by consuming the already low levels of endogenous C1 inhibitor in HAE patients. Patients with C1 inhibitor deficiency experience recurrent, unpredictable, debilitating, and potentially life threatening attacks of inflammation affecting the larynx, abdomen, face, extremities and urogenital tract. Patients with HAE experience approximately 20 to 100 days of incapacitation per year. There are estimated to be at least 6,500 people with HAE in the United States.
For more information on HAE, visit the U.S. HAE Association's website at: www.haea.org, and the International HAE Association's website at: www.haei.org.
About ViroPharma Incorporated
ViroPharma Incorporated is an international biopharmaceutical company committed to developing and commercializing innovative products for physician specialists to enable the support of patients with serious diseases for which there is an unmet medical need, and providing rewarding careers to employees. ViroPharma commercializes Cinryze® (C1 esterase inhibitor [human]) for routine prophylaxis against angioedema attacks in adolescent and adult patients with hereditary angioedema (HAE). ViroPharma commercializes Vancocin®, approved for oral administration for treatment of antibiotic-associated pseudomembranous colitis caused by Clostridium difficile and enterocolitis caused by Staphylococcus aureus, including methicillin-resistant strains (for prescribing information on ViroPharma's commercial products, please download the package inserts at http://www.viropharma.com/Products.aspx). ViroPharma currently focuses its drug development activities in diseases including C1 esterase inhibitor deficiency and C. difficile infection.
ViroPharma routinely posts information, including press releases, which may be important to investors in the investor relations and media sections of our company's web site, www.viropharma.com. The company encourages investors to consult these sections for more information on ViroPharma and our business.
Forward Looking Statements
Certain statements in this press release contain forward-looking statements that involve a number of risks and uncertainties. Forward-looking statements provide our current expectations or forecasts of future events. There can be no assurance that that the data presented during the 2010 International Scientific Conference of the World Allergy Association (WAO) regarding Cinryze is predictive of how Cinryze will perform in commercial usage. Cinryze is currently available only in the United States. Cinryze is not approved in the U.S. for acute treatment of attacks nor has the safety and effectiveness of Cinryze been established in pediatric patients with HAE. We cannot assure that current or future studies with Cinryze in the patient populations described in the WAO presentations may demonstrate the safety and efficacy profile of Cinryze. The EMA may view the data regarding the use of Cinryze for acute treatment and / or prevention of HAE we have submitted in the MAA as insufficient or inconclusive, request additional data, require additional clinical studies, delay any decision past the time frames anticipated by us, limit any approved indications, deny the approval of Cinryze for acute treatment and / or prevention of HAE or approve a competing product which has been granted orphan drug designation thereby preventing Cinryze from reaching the European market. For example, in June 2009, the U.S. FDA issued a complete response letter and requested an additional clinical study, due to their opinion that the placebo controlled study submitted in support of the sBLA for acute treatment of HAE lacked robustness. These factors, and other factors, including, but not limited to those described in our annual report on Form 10-K for the year ended December 31, 2009 and 10-Q filings for the quarters ended March 31, 2010, June 30, 2010 and September 30, 2010 filed with the Securities and Exchange Commission, could cause future results to differ materially from the expectations expressed in this press release. The forward-looking statements contained in this press release are made as of the date hereof and may become outdated over time. ViroPharma does not assume any responsibility for updating any forward-looking statements. These forward looking statements should not be relied upon as representing our assessments as of any date subsequent to the date of this press release.
SOURCE ViroPharma Incorporated