Australia's Pharmaxis is scheduled to make its case for a new cystic fibrosis therapy in front of an FDA advisory committee. But based on the agency staff review out earlier this week, investigators will likely get grilled about a high dropout rate in two key studies and the mixed efficacy data they delivered.
The spotlight is being fixed on Bronchitol (mannitol), which is designed to shrink the amount of mucus that builds up in the lungs of CF patients. It's already being rolled out in Europe and now Pharmaxis wants a shot at the 30,000 CF patients who live in the U.S.
The company has been upbeat about its chances this week, but David Pittman at MedPage Today notes that FDA staffers raised questions about the mixed efficacy data. In one study the CF drug arm hit a statistically significant boost in FEV1--forced expiratory volume per second, a key measure of lung function--after 26 weeks of dosing at 400mg of inhaled powder. In a separate trial, though, the data fell short of statistical significance.
The staffers were particularly leery about the statistical impact of a high dropout rate. As MedPage Today notes, about a third of the patients in the drug arm dropped out of one study, though 85% made it through another. But if you count dropouts as failures, neither study achieves statistical significance. And a post hoc attempt to reconcile the data on Pharmaxis's part didn't sit well with the FDA.
It's not unusual, of course, for a staff review to highlight the negative about experimental drugs. The agency wants its experts to ask tough questions, even if insiders are leaning toward an approval. Pharmaxis will find out soon whether it can clear this important hurdle as it pushes for formal marketing approval.