FDA grants priority review of Cinryze C1 inhibitor as treatment for acute attacks of hereditary angioedema

ViroPharma Incorporated has announced that the U.S. Food and Drug Administration (FDA) has granted priority review for Cinryze C1 Inhibitor (human) as a treatment for acute attacks of Hereditary Angioedema (HAE).

The supplemental Biologics License Application (sBLA), submitted to the FDA on December 1, 2008, was based on a re-analysis and resubmission of data from a pivotal Phase 3 acute treatment study of Cinryze and interim data from an ongoing open label acute study of the drug.

Cinryze was approved on October 10, 2008 for routine prophylaxis against angioedema attacks in adolescent and adult patients with HAE.

Priority review is granted by the FDA for a treatment that addresses an unmet medical need and demonstrates improvement over existing therapies. The FDA expedites the approval process for applications granted priority review from ten to six months. The PDUFA date for the sBLA is June 3, 2009.

"The priority review designation marks a positive step in bringing another use of Cinryze closer to the patients who suffer acute attacks of hereditary angioedema," commented Vincent Milano, ViroPharma's president and chief executive officer. "We look forward to working with the FDA on approval so that we can help this additional group of patients."

The administration of Cinryze produced beneficial effects in treating acute HAE attacks in these studies. The safety profile was similar to that observed with the use of Cinryze for routine prophylaxis of angioedema attacks in patients with HAE, the currently approved indication. Overall, more than 9,000 doses of Cinryze have been administered to over 180 patients in all controlled and open label clinical studies of Cinryze for both acute treatment and routine prophylaxis against angioedema attacks.

The Phase 3 acute treatment study was a randomized, double blind, placebo controlled multi-center trial in 71 patients evaluating the safety and efficacy profile of Cinryze for treatment of HAE attacks. The primary efficacy measure in the pivotal Phase 3 acute treatment study was the time from initial treatment to the start of unequivocal relief of the defining symptom. Based on the primary efficacy variable, in the All Randomized (ITT) Dataset, the likelihood of a patient having the start of unequivocal relief of the defining symptom was 2.048 times greater in the Cinryze treatment group than in the placebo treatment group (p=0.048). The median time to the start of unequivocal relief of the defining symptom was shorter in subjects in the Cinryze treatment group (two hours) than in subjects in the placebo treatment group (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 or intubation. Cinryze was generally well tolerated. There were no deaths or serious adverse reactions related to Cinryze administration, or discontinuations due to treatment-emergent adverse events. In the analysis of 447 acute attacks in 82 patients, open label Cinryze administration provided substantial relief of the defining symptom in 93.4 percent of the attacks within four hours of injection, with a median time to onset of relief of 30 minutes. There was no observed loss of effectiveness over multiple administrations of Cinryze for subsequent HAE attacks.

About Cinryze C1 Inhibitor (human)

Cinryze is a highly purified, pasteurized and nanofiltered plasma-derived C1 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. Cinryze has not been approved for acute treatment in the United States or any other jurisdiction.

Cinryze has been generally well tolerated. 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 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 patients 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.

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 unrestricted, 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 4600 people with HAE in the United States.