Date: 2016-10-06
Type of
information: Results
phase: preclinical
Announcement: results
Company: PTC Therapeutics (USA - NJ)
Product: Translarna™ (ataluren)
Action
mechanism:
- protein restauration therapy/inducer of ribosomal readthrough on nonsense mutation mRNA stop codons. Ataluren (3-[5-(2-fluoro-phenyl)-[1,2,4]oxadiazole-3-yl]-benzoic acid) is an investigational new drug designed to enable the production of functional dystrophin protein in the muscle cells of patients with genetic disorders due to a nonsense mutation. Ataluren is designed to allow the ribosome to ignore the premature stop signal and continue translation of the mRNA, resulting in formation of a functioning protein. Ataluren does not cause the ribosome to read through the normal stop signal.
Disease: non-ambulatory nonsense mutation Duchenne muscular dystrophy patients (nmDMD)
Therapeutic
area: Rare diseases - Genetic diseases
Country:
Trial
details:
Latest
news:
- • On October 6, 2016, PTC Therapeutics announced new data supporting the potential benefit of ataluren in preserving lung function in non-ambulatory nonsense mutation Duchenne muscular dystrophy patients (nmDMD). The results, which are being presented as part of a company-sponsored symposium, are based on PTC's analyses of lung function data from one of PTC's ongoing open-label extension studies (Study 019) versus natural history data from a comparable non-ambulatory cohort. DMD patients experience progressive dysfunction of respiratory muscles, in particular the diaphragm, leading to respiratory failure which is the primary cause of death. Pulmonary function in DMD patients has historically been assessed using forced vital capacity (FVC), a measure of lung function that correlates with disease progression and mortality.i FVC tends to peak at an earlier age in DMD patients and then decline more rapidly than in healthy individuals. The analysis of ataluren's impact on preservation of lung function is based on FVC, a marker of respiratory insufficiency which progresses with age. The results presented are from a preliminary assessment of pulmonary function in non-ambulatory patients in Study 019 (n = 53). The data were compared with an external control group of patients not receiving ataluren ("untreated") in a long-term DMD natural history study performed by the Cooperative International Neuromuscular Research Group (CINRG) (n = 114). The CINRG cohort was matched using the following criteria: non-ambulatory (requiring wheelchair use), ? 25 years old, with ? 24 months of corticosteroid use. To reflect the standard of care available during Study 019, only CINRG data from 2012 onward were included.
- In order to apply a linear regression model to the analysis, FVC data were log-transformed to achieve a normal distribution. A piecewise linear regression model, which accounts for peak lung function, was utilized. In the untreated natural history cohort, FVC peaked at a mean age of 12.5 years and then declined thereafter. In comparison, ataluren-treated patients achieved peak FVC at a mean age of 16.5 years, a difference of 4 years over the untreated patients. In addition, absolute FVC was 13.8% higher in ataluren-treated patients compared with untreated patients (nominal p = 0.005), which suggests a slower progression of loss in lung function in ataluren-treated patients. These historically controlled, matched analyses provide insight into the potential pulmonary benefits realized by non-ambulatory ataluren-treated patients versus untreated DMD patients.
Is
general: Yes
