Empresa anuncia os bons resultados com a droga PTC 124 para tratamento da distrofia muscular de Duchenne
Inglaterra – no encontro dos pais realizado na Inglaterra hoje a empresa PTC anunciou os resultados preliminares da fase II com o uso do PTC124 uma droga dada por via oral para tratamento da mutação de ponto na distrofia muscular de Duchenne (cerca de 1/3 dos pacientes tem mutação de ponto). Os resultados mostraram que houve produção de distrofina em muitas crianças e redução dos níveis da enzima CK; os efeitos colaterais foram pequenos e não necessitaram da suspensão da medicação. Não houve uma avaliação física das crianças mas muitas relataram melhora da força muscular (o tratamento foi feito por 28 dias). As análises continuam a ser feitas e o resultado final será divulgado no começo de 2007 e esperá-se para 2007 um novo estudo, com tratamento por tempo maior, com doses diferentes (talvez maiores) e com maior número de crianças. É um resultado preliminar mais muito promissor. Mais informações sobre este tratamento pode ser lido nestes links:
Readthrough strategies for stop codons in Duchenne muscular dystrophy
O resumo das informações dadas pelo laboratório pode ser lido abaixo:
SOUTH PLAINFIELD, NJ – October 21, 2006 – PTC Therapeutics, Inc. (PTC), a biopharmaceutical company focused on the discovery and development of small-molecule drugs targeting post-transcriptional control processes, today announced encouraging data from a Phase 2 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 today at the PPUK 4th International DMD Conference in London, England.
“These results are the first example of an oral therapy addressing the underlying cause of DMD by restoring dystrophin production,” said Dr. Richard Finkel, Director of the Neuromuscular Program, Children’s Hospital of Philadelphia, PA, one of the trial’s lead investigators. “There are limited therapeutic options for patients living with DMD, and these data strongly indicate PTC124 warrants further clinical investigation in this patient population, which has a great unmet medical need.”
Langdon Miller, M.D., Chief Medical Officer, PTC, stated, “These preliminary results in patients with DMD provide confirmation of proof of concept that PTC124 can induce ribosomal readthrough of nonsense mutations as an approach to treating genetic disorders. Given that PTC124 was very well-tolerated and activity was observed at lower-than-expected plasma concentrations, we are amending this trial to evaluate higher dose levels and the potential to further increase dystrophin expression.”
“In the first half of 2007, we expect to present the final data set from this Phase 2 clinical trial and meet with regulatory authorities to determine the next steps for further clinical development of PTC124. Following these discussions, we hope to initiate longer-term clinical trials for PTC124 in 2007,” said Dr. Miller.
Patients with DMD who 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.
Patients included in the interim analysis were enrolled at three clinical sites in the United States: Children’s Hospital of Philadelphia, Philadelphia, Pennsylvania; Cincinnati Children’s Hospital Medical Center, Cincinnati, Ohio; and the University of Utah, Salt Lake City, Utah. 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 of 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.
PTC124 was well tolerated among the 26 patients included in the study. Potentially drug-related adverse events were infrequent, mild to moderate in severity, did not result in therapy interruptions or discontinuations, and were reversible. There were no safety concerns based on physical examinations, vital sign measurements, electrocardiograms, or laboratory parameters. Compliance was excellent at both dose levels.
“These preliminary results are very encouraging and add to the growing body of clinical evidence supporting the potential of PTC124 as a treatment for genetic disorders due to a nonsense mutation,” said Stuart W. Peltz, Ph.D., President and Chief Executive Officer of PTC Therapeutics. “The findings in the DMD trials are consistent with the results observed in Phase 2 clinical trials of PTC124 in patients with cystic fibrosis. We intend to extend this concept into other
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