PTC THERAPEUTICS ANNOUNCES PRELIMINARY RESULTS FROM DMD STUDY

PTC Therapeutics has announced encouraging data from a Phase II clinical trial of PTC124 in patients with Duchenne muscular dystrophy (DMD) due to a nonsense mutation. The results imply pharmacological activity based on preliminary data that suggest increases in dystrophin in muscle biopsies in a number of patients and statistically significant improvements in muscle enzymes in serum. The preliminary data were presented at the PPUK International DMD Conference in London.

Patients with DMD lack dystrophin, a protein that is critical to the structural stability of muscle fibers. This Phase II multisite, 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.

Patients included in the interim analysis were enrolled at three clinical sites in the United States. In the study, patients received 28 days of PTC124 treatment at one of two dose levels. All patients were boys with a nonsense mutation in the dystrophin gene, substantially elevated serum creatine kinase and symptoms associated with DMD.

Assessment of the in vitro effects of PTC124 on dystrophin expression showed dose-dependent production of full-length dystrophin in myocytes obtained from multiple study subjects; these data suggest the potential for response across a range of early to late nonsense mutations within the dystrophin gene. Evaluation of the in vivo effects of PTC124 over the 28-day treatment course suggest an increase in dystrophin expression in muscle biopsies in a number of the boys participating in the trial, although quantitative analysis is not yet complete. Statistically significant reductions in the concentrations of muscle-derived creatine kinase levels in the blood were observed during PTC124 treatment. Although no formal questionnaire was used to collect data on changes in DMD-related symptoms, several parents and teachers reported that boys participating in the study had improvements in terms of greater activity level and increased endurance during treatment.