PTC Therapeutics Inc. (PTC), a biopharmaceutical company focused on the discovery and development of small-molecule drugs targeting post-transcriptional control processes, has announced positive interim data from a phase 2 clinical trial of PTC124 in patients with Duchenne muscular dystrophy (DMD) due to a nonsense mutation.

The results from the first two cohorts of the three-cohort study show that treatment with PTC124 was associated with increases in muscle dystrophin expression and reductions in serum creatinine kinase values in at least 50 per cent of evaluable patients. These data were presented at the 59th American Academy of Neurology (AAN) Annual Meeting.

Patients with DMD lack dystrophin, a protein that is critical to the structural stability of muscle fibers. This phase 2 multi-site, open-label, dose-ranging clinical trial is evaluating muscle dystrophin expression in patients with nonsense-mutation-mediated DMD. Blood levels of muscle-derived creatine kinase are being measured as assessments of muscle integrity. PTC124 safety, compliance, and pharmacokinetics are also being evaluated.

"These data provide clinical evidence that PTC124 treatment may address the underlying cause of DMD," said Dr Richard Finkel, director of the Neuromuscular Program, Children's Hospital of Philadelphia, PA, who presented these results today at AAN as one of the trial's lead investigators. "Development of PTC124 offers the potential for a new therapeutic option for patients with DMD due to a nonsense mutation."

Langdon Miller, MD, Chief Medical Officer of PTC, added, "We are very pleased with these additional pharmacologic proof-of-concept data from our short-term phase II clinical trial of PTC124 in patients with DMD. Based on the growing body of phase 2 clinical data, we plan to initiate longer-term clinical trials to evaluate the clinical benefit of PTC124 in patients with DMD."

The phase 2 clinical trial is being conducted at three sites in the United States namely Children's Hospital of Philadelphia, Philadelphia, Pennsylvania; Cincinnati Children's Hospital Medical Centre, Cincinnati, Ohio; and the University of Utah, Salt Lake City, Utah. In the study, patients have received 28 days of PTC124 treatment at one of three dose levels. All clinical trial participants are boys with a nonsense mutation in the dystrophin gene, substantially elevated serum creatine kinase levels, and symptoms associated with DMD.

PTC124 was well tolerated among the 26 patients included in the study. Adverse events were infrequent, mild to moderate in severity, and did not result in therapy interruptions or discontinuations. There were no safety concerns based on physical examinations, vital sign measurements, electrocardiograms or laboratory parameters. Compliance with PTC124 treatment was excellent at both dose levels.

Stuart W. Peltz, Ph.D., president and CEO of PTC Therapeutics, stated, "In addition to the clinical proof-of-concept data we disclosed late last year, these new insights provide us with further evidence supporting the potential of PTC124 in genetic disorders due to a nonsense mutation. The findings in the DMD trials are consistent with the results observed in phase II clinical trials of PTC124 in patients with cystic fibrosis and with preclinical results in the DMD mouse model that were recently published in Nature. We are eager to extend testing of this concept into other nonsense-mediated genetic disorders."