Agency said submitted results from placebo-controlled trial were not robust.
ViroPharma’s attempts to expand the use of its prophylactic against angioedema attacks into the acute setting was served a setback. FDA reported that the placebo-controlled study submitted in support of the sBLA lacked robustness, and the agency thus requires another clinical trial.
Cinryze is a highly purified, pasteurized, and nanofiltered plasma-derived C1 esterase inhibitor product. It was approved in October 2008 for routine prophylaxis against angioedema attacks in adolescent and adult patients with hereditary angioedema. During the first quarter of 2009 the drug brought in net sales of $6.7 million.
Despite the complete response letter related to the sBLA, the FDA is allowing the labeling to include self-administration for routine prophylaxis once patients are properly trained by their healthcare provider.
The sBLA was based on a reanalysis and resubmission of data from a Phase III acute treatment study and interim data from an ongoing open-label acute-setting trial. The Phase III acute treatment study was a randomized, double-blind, placebo-controlled, multicenter trial in 71 patients. The primary efficacy measure was the time from initial treatment to the start of unequivocal relief of the defining symptom. This was 2.048 times greater in the Cinryze treatment group, and the median time for relief was shorter in subjects taking Cinryze (two hours) than in subjects in the placebo treatment group (greater than four hours).
In the open-label study no patients who had acute laryngeal edema attacks required hospitalization or intubation. In the analysis of 447 acute attacks in 82 patients, open-label Cinryze administration provided relief in 93.4% of the attacks within four hours of injection, with a median time to onset of relief of 30 minutes.