PTC Therapeutics, Inc. (PTC), a biopharmaceutical company focused on the discovery, development and commercialization of small-molecule drugs targeting post-transcriptional control mechanisms, has announced encouraging data from a phase II clinical trial of PTC124 in paediatric patients with cystic fibrosis (CF) due to a nonsense mutation.

These paediatric results and additional information emerging from long-term studies support the existing data from prior short-term studies in adult CF patients. These studies show that treatment with PTC124 results in statistically significant improvements in a measure of the function of the cystic fibrosis transmembrane conductance regulator (CFTR) protein.

Patients with CF lack the CFTR protein, a chloride channel that maintains proper hydration of epithelial cells in the lung, pancreas, and liver. PTC has completed multi-site, open-label, dose-ranging phase II clinical trials in adult CF patients to determine whether PTC124 can induce production of active CFTR protein. Studies in the US and Israel evaluated nasal transepithelial potential difference (TEPD) as a surrogate for CFTR protein production in adult CF patients. Across the two studies, at both PTC124 dose levels tested, TEPD assessments showed statistically significant improvements of mean CFTR-dependent chloride secretion in the airways.

PTC is currently conducting a third, open-label, dose-ranging phase II clinical trial in paediatric CF patients at l'Hôpital Necker-Enfants Malade, Paris, France to determine whether PTC124 can induce production of active CFTR protein. In the trial, patients receive two sequential two-week courses of treatment. Patients have been randomized to receive either a low or high dose of PTC124 followed by two weeks of rest and then are crossed over to the other dose level for an additional two weeks of therapy. Eleven patients have completed the study and data from these patients were available for inclusion in the initial analysis. Across both dose levels, statistically significant improvements were seen in CFTR chloride-channel function as measured by TEPD.

"Our initial observations in a paediatric population confirm the findings from the previous studies in older CF patients," said Isabelle Sermet-Gaudelus, MD, Ph.D., principal investigator at l'Hôpital Necker-Enfants Malade, Paris, France. "Normalization of CFTR-mediated chloride secretion was observed in several of the children, indicating that PTC124 continues to demonstrate significant potential as a treatment for patients with CF. Based on the enthusiasm generated by these data, we have recently added two new study sites in Belgium in order to expand the evaluation of PTC124 across a larger paediatric population."

Eitan Kerem, MD, head of paediatrics and the CF Center at the Hadassah University Hospital in Mount Scopus, Jerusalem also commented on longer-term studies that he has been leading in Israel. "Based on the positive results we observed during our initial study with two-week treatment periods, we have analyzed preliminary data from a three-month extension study evaluating the longer-term effect of PTC124 in patients with nonsense-mutation-mediated CF. We have seen encouraging evidence of sustained CFTR chloride-channel function and improvements in symptoms of CF, such as coughing, which we believe may be predictive of longer-term clinical benefit. We look forward to presenting the full data from this trial next year".

"We are very pleased to see the evidence of drug activity reported at last year's North American Cystic Fibrosis Conference reproduced by additional investigators in a paediatric population," said Langdon Miller, MD, chief medical officer of PTC. "We are also encouraged by the findings of the Israeli three-month study. We believe these confirmatory results, coupled with supportive safety data in more than 50 patients participating in the phase II trial programme, can lead to initiation of longer-term trials to evaluate the clinical benefit of PTC124 in patients with CF."