ViroPharma Announces Availability of Cinryze(TM) (C1 Esterase Inhibitor [Human]) Final Open-Label Data

EXTON, Pa., May 17 /PRNewswire-FirstCall/ -- ViroPharma Incorporated (Nasdaq: VPHM) today announced the availability of final data from Open-Label studies of Cinryze™ (C1 Esterase Inhibitor [Human]) in preventing and treating attacks of hereditary angioedema (HAE) on the U.S. National Institutes of Health's online clinical trial registry, www.clinicaltrials.gov. The data from the CHANGE 3 prophylaxis study are available now; the data from the CHANGE 2 acute treatment study will be available at the same website in the coming weeks.  The company expects the complete data set to be presented at a scientific meeting later this year and in subsequent publications in peer-reviewed journals.

Cinryze was approved by the U.S. Food and Drug Administration in October 2008 for routine prophylaxis against angioedema attacks in adolescent and adult patients with HAE.  Cinryze is not approved in the U.S. for acute treatment of attacks.    

"We are excited about the strength of these data in support of the efficacy and safety of Cinryze, and are happy to see them available online," commented Colin Broom, M.D., ViroPharma's chief scientific officer.  "Our open label experience with the therapy, outside the confines of controlled pivotal clinical studies, has shown that Cinryze therapy can change the lives of HAE patients and their families. For example, prophylaxis with Cinryze in the open label prevention study dramatically reduced the median frequency of attacks from three times per month to less than three attacks per year.  Our goal as a company is to improve the lives of the patients suffering from HAE, and it is clear that Cinryze accomplishes that goal for patients who choose prophylaxis against their HAE attacks as their means to regain control of their lives."

Open-Label C1 Esterase Inhibitor for the Prevention of Acute HAE Attacks

The CHANGE 3 study was performed to evaluate the safety and efficacy of prophylactic use of Cinryze for the prevention of attacks of HAE.  One hundred forty six (146) HAE patients were enrolled in this study and were included in the analysis of the primary efficacy outcome measure.  The vast majority of the patients enrolled in the study have transitioned to commercial Cinryze. Seventy-nine (79) patients completed the study; most of those not completing the study did so because they transitioned to commercial Cinryze before the end of the study.  Per protocol, patients received 1,000U of Cinryze administered intravenously every three to seven days.

The primary efficacy outcome measure was the frequency of all HAE attacks that occurred during prophylaxis with Cinryze.  Prior to initiating prophylactic therapy with Cinryze, patients enrolled in the study had a median of 3.00 HAE attacks per month. During prophylaxis with Cinryze, over a median of 244 days, enrolled patients had a median of 0.21 HAE attacks per month.

For patients that received Cinryze prophylaxis for at least one year, the degree of protection from HAE attacks was maintained over the one year period.

In this study, there were no serious adverse events (SAEs) considered related to Cinryze.  No subjects were discontinued from Cinryze due to an adverse event, and there were no adverse trends observed in vital signs. Among the 74 subjects tested, there were no subjects who had detectable anti-C1-INH antibodies following Cinryze administration.

Open-Label C1 Esterase Inhibitor for the Treatment of Acute HAE Attacks

The CHANGE 2 study was performed to evaluate the safety and efficacy of repeat use of Cinryze for treatment of attacks of HAE.  A total of 113 subjects were enrolled in the study; 101 subjects received Cinryze for treatment of one or more HAE attacks and were analyzed for efficacy.  Forty three (43) patients completed the study; the majority of the patients not completing the study did so because they transferred to the open-label prophylaxis study.  Per protocol, patients received 1,000U of Cinryze administered intravenously for treatment of HAE attacks.  If there was inadequate response to treatment within one hour after the first dose, a second 1,000U dose could be administered.

The primary efficacy outcome measure was the proportion of HAE attacks with substantial relief of the defining symptom within four hours of initial treatment with Cinryze. Substantial relief was attained in eighty seven (87) percent of attacks, when a conservative definition of response was applied so that all patients with incomplete data were considered treatment failures. Using a less conservative definition of substantial relief as either three consecutive reports of symptom improvement or improvement of the defining symptom followed by cessation of symptom assessments, ninety five (95) percent of HAE attacks were substantially relieved within four hours of initial treatment. Eighty-four (84) laryngeal attacks occurred during this study; none required intubation following treatment with Cinryze.

Data were also analyzed for patients who received Cinryze treatment for multiple attacks of HAE; there was no loss of effectiveness of Cinryze with subsequent repeat administration.

In this study, there were no serious adverse events (SAEs) considered related to Cinryze.  No subjects were discontinued from Cinryze due to an adverse event, and there were no adverse trends observed in vital signs. There was no evidence for the development of anti-C1-INH antibodies following repeated Cinryze administration.

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 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. A Medicinal Authorization Application (MAA) for Cinryze for acute treatment and routine prophylaxis of acute attacks in patients with HAE has been accepted for filing by the European Medicines Agency (EMA) and currently is undergoing review.

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. Severe hypersensitivity reactions may occur. Thrombotic events have occurred in patients receiving high dose off-label C1 esterase inhibitor therapy well above the approved treatment dosage regimen. 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 plasma donors for prior exposure to certain virus infections and by manufacturing steps to reduce the risk of viral transmission including pasteurization and nanofiltration.

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 6,000 people with HAE in the United States.

For more information on HAE, visit the U.S. HAE Association's website at: http://www.haea.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, http://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 from the open label studies with Cinryze is predictive of how Cinryze will perform in commercial usage or that Cinryze therapy can change the lives of HAE patients and their families.  Cinryze is not approved in the U.S. for acute treatment of attacks. 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 for the quarter ended March 31, 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