Ataluren in Patients With Nonsense Duchenne Muscular Dystrophy



Title: Ataluren in patients with nonsense mutation Duchenne muscular dystrophy (ACT DMD): a multicentre, randomised, double-blind, placebo-controlled, phase 3 trial

McDonald, CM et al.


 

What You Need to Know:

In ambulatory boys with nonsense mutation Duchenne muscular dystrophy (DMD), no significant differences were seen in the change in 6-minute walk distance (6MWD) after treatment with ataluren compared to placebo, except in patients with baseline 6MWD of 300-400 meters.

Trial Design:

  • Double-blind, placebo-controlled, phase 3 study evaluated the safety and efficacy of ataluren in 7-16 year old boys with nonsense mutation DMD and a 6MWD baseline of 150 m and 80% of the predicted normal value for age and height
  • 230 patients were randomized (1:1) to receive 40 mg/kg/day of ataluren administered orally three times daily (n=115) or placebo (n=115)
  • Primary endpoint: 6MWD change from baseline to week 48; analyzed using the intention-to-treat population
  • Subgroup analysis of the primary endpoint: conducted based on baseline 6MWD, “which is reflective of anticipated rates of disease progression over 1 year”

Key Outcomes:

  • Least-squares mean 6MWD change from baseline to week 48: -47.7 m (SE: 9.3) for patients receiving ataluren vs -60.7 m (SE: 9.3) for patients receiving placebo (difference: 13.0 m; SE: 10.4; 95% CI: -7.4, 33.4; P=0.213)
  • “The least-squares mean change for ataluren versus placebo in the prespecified subgroups was −7·7 m (SE 24·1, 95% CI −54·9 to 39·5; p=0·749) in the group with a 6MWD of less than 300 m, 42·9 m (15·9, 11·8–74·0; p=0·007) in the group with a 6MWD of 300 m or more to less than 400 m, and −9·5 m (17·2, −43·2 to 24·2; p=0·580) in the group with a 6MWD of 400 m or more”
  • Majority of treatment-emergent adverse events experienced by patients receiving ataluren were reported as mild to moderate in severity
  • Serious adverse events: experienced by 3% of patients (n=8; 4 patients in each group)
  • 1 serious adverse event was deemed possibly related to treatment (abnormal hepatic function experienced by 1 patient in the placebo group)