FDA reviewers question Bronchitol efficacy

FDA reviewers said efficacy results for Bronchitol mannitol from Pharmaxis Ltd. (ASX:PXS; Pink:PXSLY) are "inconsistent," as the product met the primary endpoint in only one of two Phase III trials to manage cystic fibrosis (CF). Specifically, the reviewers concluded Bronchitol significantly improved the proportion of patients with an increase from baseline in forced expiratory volume in one second (FEV1) vs. placebo in Study CF302 -- but not Study CF301 -- based on an intent-to-treat (ITT) analysis. The comments came in briefing documents released ahead of Wednesday's Pulmonary-Allergy Drugs Advisory Committee meeting to discuss an NDA for the product.

Pharmaxis proposed using a modified intent-to-treat (mITT) analysis that excluded patients who dropped out prior to week six, which it said showed Bronchitol met the primary endpoint in CF301 and approached significance in CF302 (p<0.001 and p=0.059, respectively). However, the reviewers concluded that excluding "frequent and treatment-related early discontinuations" in the treatment arm meant the mITT analyses were not an "accurate reflection" of Bronchitol's efficacy. ...