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.
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.
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.
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.. Our actual results may vary significantly from these forward-looking statements. The commercialization of pharmaceutical products is subject to risks and uncertainties. The data that were discussed at the ACAAI meeting 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, 2011 and 10-Q filings for the quarters ended March 31, 2012, June 30, 2012, and 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