10 research outputs found
Meta-analyses of ataluren randomized controlled trials in nonsense mutation Duchenne muscular dystrophy.
Aim: Assess the totality of efficacy evidence for ataluren in patients with nonsense mutation Duchenne muscular dystrophy (nmDMD).
Materials & methods: Data from the two completed randomized controlled trials (ClinicalTrials.gov: NCT00592553; NCT01826487) of ataluren in nmDMD were combined to examine the intent-to-treat (ITT) populations and two patient subgroups (baseline 6-min walk distance [6MWD] \u3e= 300-\u3c400 or \u3c400 m). Meta-analyses examined 6MWD change from baseline to week 48.Results:Statistically significant differences in 6MWD change with ataluren versus placebo were observed across all three meta-analyses. Least-squares mean difference (95% CI): ITT (n = 342), +17.2 (0.2-34.1) m, p = 0.0473; \u3e= 300-\u3c400 m (n = 143), +43.9 (18.2-69.6) m, p = 0.0008; \u3c400 m (n = 216), +27.7 (6.4-49.0) m, p = 0.0109.
Conclusion: These meta-analyses support previous evidence for ataluren in slowing disease progression versus placebo in patients with nmDMD over 48 weeks. Treatment benefit was most evident in patients with a baseline 6MWD \u3e= 300-\u3c400 m (the ambulatory transition phase), thereby informing future trial design
Ataluren treatment of patients with nonsense mutation dystrophinopathy
Introduction: Dystrophinopathy is a rare, severe muscle disorder, and nonsense mutations are found in 13% of cases. Ataluren was developed to enable ribosomal readthrough of premature stop codons in nonsense mutation (nm) genetic disorders. Methods: Randomized, doubleâblind, placeboâcontrolled study; males â„5 years with nmâdystrophinopathy received study drug orally 3 times daily, ataluren 10, 10, 20 mg/kg (Nâ=â57); ataluren 20, 20, 40 mg/kg (Nâ=â60); or placebo (Nâ=â57) for 48 weeks. The primary endpoint was change in 6âMinute Walk Distance (6MWD) at Week 48. Results: Ataluren was generally well tolerated. The primary endpoint favored ataluren 10, 10, 20 mg/kg versus placebo; the week 48 6MWD Îâ=â31.3 meters, post hoc Pâ=â0.056. Secondary endpoints (timed function tests) showed meaningful differences between ataluren 10, 10, 20 mg/kg, and placebo. Conclusions: As the first investigational new drug targeting the underlying cause of nmâdystrophinopathy, ataluren offers promise as a treatment for this orphan genetic disorder with high unmet medical need
Deflazacort vs prednisone treatment for Duchenne muscular dystrophy: A metaâanalysis of disease progression rates in recent multicenter clinical trials
Introduction: In this study we characterized disease progression over 48âweeks among boys receiving deflazacort vs prednisone/prednisolone placebo arm treatment in two recent Duchenne muscular dystrophy (DMD) clinical trials. /
Methods: Ambulatory boys with DMD receiving placebo in the phase 3 ataluren (N = 115) and tadalafil (N = 116) trials were included. The trials required at least 6âmonths of prior corticosteroid use and stable baseline dosing. Associations between corticosteroid use and 48âweek changes in ambulatory function were estimated using mixed models. Adjusted differences between corticosteroid groups were pooled in a metaâanalysis. /
Results: In the metaâanalysis, deflazacortâtreated patients vs prednisone/prednisoloneâtreated patients experienced, on average, lower declines of 28.3 meters on 6âminute walk distance (95% confidence interval [CI], 5.7, 50.9; 2.9âseconds on rise from supine [95% CI, 0.9, 4.9âseconds]; 2.3âseconds on 4âstair climb [95% CI, 0.5, 4.1âseconds]; and 2.9 [95% CI, 0.1, 5.8] points on the North Star Ambulatory Assessment linearized score). /
Discussion: Deflazacortâtreated patients experienced significantly lower functional decline over 48âweeks