- Publication Describes Safety and Efficacy Profile of Cinryze® (C1 esterase inhibitor [human]) in Children and Adolescents Receiving 2,237 Infusions -
EXTON, Pa., Jan. 16, 2013 /PRNewswire/ -- ViroPharma Incorporated (Nasdaq: 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 Lumryet 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 Study
Four pediatric patients (ages 9 to 17 years) enrolled in and completed the pivotal prophylaxis trial. Children had a nearly 2‑fold 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 Study
Twenty-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.
Eight 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 72 hours 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 Attacks
Twelve pediatric patients were treated for an attack (7 Cinryze, 5 placebo) in the placebo-controlled acute-attack treatment study. Another 3 children 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 4 hours 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.
In 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, 9 of 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.
No serious or severe adverse events were considered by the investigator to be related to Cinryze, and no adverse events led to treatment discontinuation. There was no evidence of human immunodeficiency virus (HIV) or viral hepatitis transmission or development of clinically relevant anti-C1 INH antibodies in these studies.
Design of Sub-Group Analysis of Prospective Data
Forty-six children and adolescents ranging in age from two to 17 years received a total of 2,237 infusions of Cinryze across two randomized, placebo-controlled studies and their open-label extensions. One of the studies and its extension evaluated the use of Cinryze in acute HAE attacks, and the other evaluated its use in prophylaxis. In the pivotal acute-attack treatment trial, patients who presented to the study site within 4 hours after onset of a moderate or severe acute attack of the abdomen, face, or external genitalia were randomly assigned to intravenous infusions of placebo or Cinryze 1000 U. The pivotal prophylaxis trial consisted of 2 consecutive 12-week treatment periods during which patients received study medication for preventing HAE attacks. Patients were randomly assigned to receive intravenous infusions of 1000 U Cinryze or placebo every 3 to 4 days.
"Through an analysis of the largest compilation of pediatric patient data from prospective HAE clinical studies, we were able to determine that the safety and efficacy profile of Cinryze in this pediatric subpopulation were similar to those seen in the overall trial population," commented Dr. William Lumry, Medical Director, Asthma and Allergy Research Associates in Dallas, Tx. "Though no drugs are currently approved for children with HAE, taken together, these data offer a substantive body of evidence supporting the clinical utility of Cinryze in pediatric patients with hereditary angioedema."
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.
Severe hypersensitivity reactions to Cinryze may occur. Thrombotic events have occurred in patients receiving Cinryze, 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 in clinical trials associated with Cinryze were rash, headache, nausea, erythema, phlebitis and local reactions at the injection site. Adverse events of sinusitis and upper respiratory infection also were observed in clinical trials. No drug-related serious adverse events (SAEs) were reported in clinical trials.
Please visit http://www.viropharma.com/products/cinryze.aspx for the full U.S. Prescribing Information; the prescribing information for other countries can be found at www.viropharma.com.
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 and at least 10,000 people in the European Union.
For more information on HAE, visit the U.S. HAE Association's website at www.haea.org and the HAEi's (International Patient Organization for C1 Inhibitor Deficiencies) website at www.haei.org.
About ViroPharma Incorporated
ViroPharma Incorporated is an international biopharmaceutical company committed to developing and commercializing novel solutions for physician specialists to address unmet medical needs of patients living with diseases that have few if any clinical therapeutic options. ViroPharma is developing a portfolio of therapeutics for rare and Orphan diseases including C1 esterase inhibitor deficiency, Friedreich's Ataxia, and adrenal insufficiency, cytomegalovirus (CMV); and recurrent C. difficile infection (CDI). Our goal is to provide rewarding careers to employees, to create new standards of care in the way serious diseases are treated, and to build international partnerships with the patients, advocates, and health care professionals we serve. ViroPharma's commercial products address diseases including hereditary angioedema (HAE), seizures, adrenal insufficiency and C. difficile-associated diarrhea (CDAD); for full U.S. prescribing information on our products, please download the package inserts at http://www.viropharma.com/Products.aspx; the prescribing information for other countries can be found at www.viropharma.com.
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.
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. Forward-looking statements in this press release include statements regarding the therapeutic use, safety, efficacy, tolerability and potential of Cinryze in children and adolescents. Our actual results could differ materially from those results expressed in, or implied by, these forward-looking statements. The commercialization of pharmaceutical products is subject to risks and uncertainties. The data that were discussed in The Journal of Pediatrics article are subject to different interpretations and may not be predictive of the results of any individual's results or of how Cinryze performs in commercial usage. 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, 2012 and 10-Q for the quarter ended September 30, 2012 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