Lung Function in Ataluren-Treated, Nonambulatory Patients with Nonsense Mutation Duchenne Muscular Dystrophy from a Long-Term Extension Trial

 

Background/Purpose: The effects of Ataluren on lung function in nonambulatory boys with nonsense mutation Duchenne muscular dystrophy (nmDMD) were assessed as part of an open-label, long-term follow-up and safety trial (NCT01557400, study 019).

Methods: Data from patients in study 019, who were receiving Ataluren 40 mg/kg/day, were compared with data from patients not receiving Ataluren (“untreated”) from a long-term DMD natural history study (NCT00468832; Cooperative International Neuromuscular Research Group [CINRG]). Patient populations were matched: nonambulatory (requiring wheelchair use), ≤ 25 years old, with ≥ 24 months of corticosteroid use. Only CINRG data from 2012 onward were included. Data were analyzed using piecewise linear regression. Absolute FVC was assessed.

Results: Overall, 114 patients from the CINRG study and 53 patients from study 019 were included (mean age: 15.9 years, 14.1 years; mean baseline absolute FVC: 1.74 L, 2.03 L [CINRG, 019, respectively]). As expected, absolute FVC increased with age in untreated patients until 12.5 years; after this breakpoint, absolute FVC tended to decrease with increasing age. In comparison, the breakpoint in Ataluren-treated patients was 16.5 years. Using the geometric mean log FVC, adjusted for within-patient correlation using a repeated measures analysis of variance, a difference of 13.8% in predicted absolute FVC was seen in favor of Ataluren-treated patients compared with untreated patients (p = 0.005).

Conclusion: In summary, this historically controlled, matched analysis shows preservation of lung function in Ataluren-treated versus untreated patients with nmDMD.