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The sBLA is based on a re-analysis and resubmission of data from a pivotalPhase 3 acute treatment study of Cinryze and interim data from an ongoing openlabel acute study of the drug. The administration of Cinryze was effective intreating acute HAE attacks in these studies. The safety profile was similar tothat observed with the use of Cinryze for routine prophylaxis of angioedemaattacks in patients with HAE, the currently approved claim. Overall, morethan 9,000 doses of Cinryze have been administered to over 180 patients in allcontrolled and open label clinical studies of Cinryze for both acute treatmentand routine prophylaxis against angioedema attacks.
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The Phase 3 acute treatment study was a randomized, double blind, placebocontrolled multi-center trial in 71 patients evaluating the safety andefficacy of Cinryze for treatment of HAE attacks. The primary efficacymeasure in the pivotal Phase 3 acute treatment study was the time from initialtreatment to the start of unequivocal relief of the defining symptom. Basedon the primary efficacy variable, in the All Randomized (ITT) Dataset, thelikelihood of a patient having the start of unequivocal relief of the definingsymptom was 2.048 times greater in the Cinryze treatment group than in theplacebo treatment group (p=0.048). The median time to the start ofunequivocal relief of the defining symptom was shorter in subjects in theCinryze treatment group (two hours) than in subjects in the placebo treatmentgroup (greater than four hours).
In the open label study of Cinryze as treatment for acute attacks of HAE,no patients who had acute laryngeal edema attacks required hospitalization orintubation. Cinryze was generally well tolerated. There were no deaths orserious adverse reactions related to Cinryze administration, ordiscontinuations due to treatment-emergent adverse events. In the analysis of447 acute attacks in 82 patients, open label Cinryze administration providedsubstantial relief of the defining symptom in 93.4 percent of the attackswithin four hours of injection, with a median time to onset of relief of 30minutes. There was no observed loss of effectiveness over multipleadministrations of Cinryze for subsequent HAE attacks.
"Routine prophylaxis against angioedema attacks is beneficial for many HAEpatients, and an FDA-approved medication to treat acute attacks also would beimportant in managing this devastating disease," said Robert Pietrusko,Pharm.D., ViroPharma's vice president, global regulatory affairs and quality."We've made great strides in recent weeks with the approval of Cinryze and thelaunch of our patient access program CINRYZESolutions(TM) to assure itsavailability for all patients who are in need of this critical therapy. We arealso pleased to have made this acute treatment submission this year."
About Cinryze C1 Inhibitor (human)
Cinryze is a highly purified, pasteurized and nanofiltered plasma-derivedC1 inhibitor product that has been approved by FDA for routine prophylaxisagainst angioedema attacks in adolescent and adult patients with HAE. C1inhibitor therapy has been used acutely for more than 30 years in Europe totreat patients with C1 inhibitor deficiency. Cinryze has not been approvedfor acute treatment in the United States or any other jurisdiction.
Cinryze has been well tolerated. The most common adverse reactionsobserved have been upper respiratory infection, sinusitis, rash and headache.No drug-related serious adverse events (SAEs) have been observed in clinicaltrials. Severe hypersensitivity reactions may occur. Thrombotic events haveoccurred in patients receiving high dose off-label C1 inhibitor therapy wellabove the approved treatment dosage regimen. With any blood or plasma derivedproduct, there may be a risk of transmission of infectious agents, e.g.viruses and, theoretically, the CJD agent. The risk has been reduced byscreening patients for prior exposure to certain virus infections and bymanufacturing steps to reduce the risk of viral transmission includingpasteurization and nanofiltration.
Cinryze is for intravenous use only. A dose of 1000 Units Cinryze can beadministered every 3 or 4 days for routine prophylaxis against angioedemaattacks in HAE patients. Cinryze is administered at an injection rate of 1 mLper minute.
About Hereditary Angioedema
HAE is a rare, severely debilitating, life-threatening genetic disordercaused by a deficiency of C1 inhibitor, a human plasma protein. This conditionis the result of a defect in the gene controlling the synthesis of C1inhibitor. C1 inhibitor maintains the natural regulation of the contact,complement, and fibrinolytic systems, that when left unrestricted, caninitiate or perpetuate an attack by consuming the already low levels ofendogenous C1 inhibitor in HAE patients. Patients with C1 inhibitor deficiencyexperience recurrent, unpredictable, debilitating, and potentially lifethreatening attacks of inflammation affecting the larynx, abdomen, face,extremities and urogenital tract. Patients with HAE experience approximately20 to 100 days of incapacitation per year. There are estimated to be at least4,600 people with HAE in the United States.
For more information on HAE, visit the U.S. HAE Association's website at:www.haea.org.
About ViroPharma Incorporated
ViroPharma Incorporated is a biopharmaceutical company dedicated to thedevelopment and commercialization of products that address serious diseasestreated by physician specialists and in hospital settings. ViroPharmacommercializes Vancocin(R) (vancomycin hydrochloride capsules, USP), approvedfor oral administration for treatment of antibiotic-associatedpseudomembranous colitis caused by Clostridium difficile and enterocolitiscaused by Staphylococcus aureus, including methicillin-resistant strains, andCinryze(TM) (C1 inhibitor (human)) for routine prophylaxis against angioedemaattacks in adolescent and adult patients with hereditary angioedema (HAE),also known as C1 inhibitor deficiency (for prescribing information onViroPharma's commercial products, please download the package inserts athttp://www.viropharma.com/Products.aspx). ViroPharma currently focuses itsdrug development activities in diseases including cytomegalovirus (CMV), HAEand C. difficile.
ViroPharma routinely posts information, including press releases, whichmay be important to investors in the investor relations and media sections ofour company's web site, www.viropharma.com. The company encourages investorsto consult these sections for more information on ViroPharma and our business.
Forward-Looking Statements
Certain statements in this press release contain forward-lookingstatements that involve a number of risks and uncertainties. Forward-lookingstatements provide the Company's current expectations or forecasts of futureevents. Forward-looking statements in this press release include statementsregarding ViroPharma's clinical development programs. Our actual results coulddiffer materially from those results expressed in, or implied by, theseforward-looking statements. The development and commercialization ofpharmaceutical products is subject to risks and uncertainties. The data thatwere submitted to the U.S. Food and Drug Administration includes data from twoseparate studies including the pivotal Phase 3 study of Cinryze in acute HAEattacks and the ongoing open-label study of Cinryze for acute treatment ofHAE, which includes partial data from an ongoing open label study. There canbe no assurance that the complete data from the open label study willdemonstrate that Cinryze successfully treats all types of acute hereditaryangioedema (HAE) attacks and may not be predictive of the results of anyfuture testing. The FDA may view the data regarding the use of Cinryze foracute treatment of HAE we have submitted as a supplemental BLA as insufficientor inconclusive, not accept our submission, request additional data, requireadditional clinical studies, delay any decision past the time framesanticipated by us, limit any approved indications, deny the approval ofCinryze for acute treatment of HAE or approve a competing product which hasbeen granted orphan drug designation thereby preventing Cinryze from reachingthe market for acute treatment of HAE. These factors, and other factors,including, but not limited to those described in ViroPharma's annual report onForm 10-K and quarterly reports on Form 10-Q filed with the Securities andExchange Commission during 2008, could cause future results to differmaterially from the expectations expressed in this press release. The forward-looking statements contained in this press release may become outdated overtime. ViroPharma does not assume any responsibility for updating any forward-looking statements.
SOURCE ViroPharma Incorporated
