Study Confirms Therapy’s Benefit for Nonsense Mutation Duchenne Muscular Dystrophy

Results from a long-term study (NCT03179631) of the protein restoration therapy ataluren (Translarna; PTC Therapeutics, Plainfield, NJ) for treating nonsense mutation Duchenne muscular dystrophy (nmDMD) confirms the drug’s effectiveness and safety.   Compared with those taking a placebo, participants treated with ataluren experienced less declines in performance on the 6-minute walk distance test and were significantly less likely to lose ambulation in general, according to research presented at the American Academy of Neurology (AAN) 2023 Annual Meeting.   

The international study (n=360) was a phase 3, randomized, double-blind, placebo-controlled 72-week trial of ataluren in patients with nmDMD followed by a 72-week open-label period. The purpose of the study was to define the long-term effects of ataluren-mediated dystrophin restoration on disease progression. Patients eligible for the study were boys with nmDMD ≥ 5 years of age who were taking corticosteroids (for a minimum of 12 months prior to study initiation) and who had a 6-minute walk distance (6MWD) ≥ 150 m. The primary objective was to determine ataluren’s effect on ambulatory function as assessed by 6MWD.

Participants were randomized in a 1:1 ratio of ataluren or placebo. They received either blinded study drug or placebo 3 times daily (TID) at morning, midday, and evening for 72 weeks, after which all participants received ataluren for an additional 72 weeks. Study assessments were performed at clinic visits every 12 weeks during the double-blind period and every 24 weeks during the open-label period.  

Results showed more favorable outcomes in those treated with ataluren in terms of mean change in 6MWD from baseline compared with those in the placebo group. The number of ITT patients who lost ambulation receiving placebo was almost double that of those receiving ataluren.

Although ataluren was well-tolerated, 85.3% of participants reported adverse events which was comparable to that reported by those taking placebo (84.7%).