ViroPharma Inc. has announced that the company submitted a supplemental Biologics License Application (sBLA) to the U.S. Food and Drug Administration (FDA) for Cinryze C1 Inhibitor (human) as a treatment for acute attacks of hereditary angioedema (HAE).
The sBLA is 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. The administration of Cinryze was effective 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 claim. 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 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.
"Routine prophylaxis against angioedema attacks is beneficial for many HAE patients, and an FDA-approved medication to treat acute attacks also would be important 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 the launch of our patient access program CINRYZESolutions to assure its availability for all patients who are in need of this critical therapy. We are also pleased to have made this acute treatment submission this year."
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 30 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.