Ataluren Helps Ambulation in Nonsense Mutation Duchenne Muscular Dystrophy

Treatment with ataluren led to weekly improvements in ambulatory function in patients with nonsense mutation Duchenne muscular dystrophy.

Ataluren has a favorable risk-benefit profile for the treatment of Duchenne muscular dystrophy (DMD), according to study results presented at the 2023 American Academy of Neurology (AAN) Annual Meeting, held from April 22 to 27, in Boston, Massachusetts.

The lack of a functional copy of dystrophin causes the severe neuromuscular disorder DMD. For patients whose dystrophin dysfunction is related to a nonsense mutation (nm) that causes a premature stop codon, the drug ataluren may be an effective therapeutic option, as it promotes readthrough of the premature stop to produce a full-length dystrophin protein.

Study 041 ( Identifier: NCT03179631) was an international, phase 3, randomized, double-blind, placebo-controlled trial evaluating ataluren. Boys aged 5 years and older with nmDMD who were receiving corticosteroids and had a 6-minute walk distance (6MWD) of 150 meters or greater were randomly assigned in a 1:1 ratio to receive ataluren or placebo. The primary outcome was the change in ambulatory function, assessed by 6MWD, after 1 or more treatments.

At baseline, the placebo and ataluren recipients were well-balanced for age, corticosteroid use, 6MWD, and time to stand from supine position.

Study 041 confirms ataluren’s favorable risk-benefit as shown in previous clinical and real-world evidence studies.

The average 6MWD changed by 0.20 meters per week among ataluren recipients in the intention-to-treat (ITT) population (P = .0248) and by 0.34 meters per week among the subset of patients who had a 6MWD of 300-400 meters at baseline (P = .0310). Relative to placebo, ataluren associated with a 21% slowing in the rate of decline in 6MWD in the ITT population and 30% slowing in decline for those with 300–400-meter 6MWD at baseline.

The proportion of patients who lost ambulation during the 72-week follow-up was nearly double in the placebo group compared with the ataluren cohort.

No probable drug-related serious adverse events were associated with ataluren. The proportion of patients who reported any adverse event was 85.3% in the ataluren treatment arm and 84.7% in the placebo arm.

The limitations of this study included the single efficacy endpoint and the lack of patient-reported outcomes.

These data supported ataluren for the treatment of nmDMD among boys and led researchers to conclude, “Study 041 confirms ataluren’s favorable risk-benefit as shown in previous clinical and real-world evidence studies.”

Disclosure: Some study authors declared affiliations with biotech, pharmaceutical, and/or device companies. Please see the original reference for a full list of authors’ disclosures.


McDonald CM, Wu S, Gulati S, et al. Safety and efficacy of ataluren in nmDMD patients from study 041, a phase 3, randomized, double-blind, placebo-controlled trial. Abstract presented at: 2023 AAN Annual Meeting; April 22-27, 2023; Boston, MA. Abstract PL5.001.