PTC THERAPEUTICS ANNOUNCES RESULTS FROM CF STUDY

PTC Therapeutics has announced the findings from two Phase II clinical trials of PTC124 in patients with cystic fibrosis (CF) due to a nonsense mutation. The results suggest that PTC124 can restore function of the cystic fibrosis transmembrane conductance regulator (CFTR) protein in airway cells and significantly reduce blood neutrophil counts that are a hallmark of the CF disease process.

Patients with CF lack the CFTR protein, a chloride channel that maintains proper hydration of epithelial cells in the lung, pancreas and liver. Patients with CF develop highly viscous secretions in these organs that result in inflammation, chronic colonization of pathogenic bacteria and progressive organ destruction. Pulmonary involvement usually causes the greatest disability as blood neutrophils migrate into the lungs, contributing to clogging of the airways.

PTC sponsored a multisite, open-label, dose-ranging, Phase II clinical trial program to determine whether PTC124 can induce production of active CFTR protein. Identical studies in the U.S. and Israel evaluated nasal transepithelial potential difference (TEPD) as a surrogate for CFTR protein production. A change in CFTR-mediated chloride transport toward normal during PTC124 treatment would suggest that PTC124 is inducing the cells to make full-length, functional CFTR protein. Patients received two sequential 14-day courses of treatment of PTC124, first at a lower and then at a higher dose level.

In the two studies, at both PTC124 dose levels tested, TEPD assessments showed statistically significant improvements of mean CFTR-dependent chloride secretion in the airways. Based on the results of the studies, PTC will be conducting a longer-term study in Israel and will initiate a pediatric clinical trial in France. Collective results from the Phase II studies will be reviewed with regulatory authorities with the intent of initiating an international Phase III trial program in 2007.