A long-term phase 3 study found that ataluren plus standard of care (SoC) delays progression of nonsense mutation Duchenne muscular dystrophy (nmDMD) and benefits ambulatory and nonambulatory patients.

Ataluren is an oral therapy for patients with nmDMD that enables ribosomes to read through a premature stop codon in mRNA, allowing translation to continue and resulting in the production of a full-length dystrophin protein.

Study 019 enrolled 94 patients (50 ambulatory and 44 nonambulatory) with DMD with various genotypes, aged 2–28 years at 20 centers in 9 countries between 2006 and 2016. Most patients were previously enrolled in prior phase 2 ataluren studies. Ataluren was dosed at 40 mg/kg/day (10 mg/kg in the morning, 10 mg/kg at midday and 20 mg/kg in the evening). The study ran for 240 weeks.

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A propensity score was used to match patients from the study with patients with similar disease characteristics in The Cooperative International Neuromuscular Research Group Duchenne Natural History Study (CINRG DNHS), a prospective, longitudinal study that provided SoC, which included corticosteroid and palliative therapies.
Treatment of patients with nmDMD with ataluren plus SoC resulted in a 2.2-year delay in age at loss of ambulation (LoA; P =0.0006) versus SoC alone in the CINRG group.

The median age at LoA for the 60 patients treated with ataluren plus SoC in Study 019 was 15.5 years, compared with 13.3 years in the matched CINRG DNHS cohort. This delay in LoA represents not only a highly meaningful prolongation of personal autonomy in daily life, but also a delay in the onset of subsequent disease milestones.

Kaplan-Meier analysis to compare the decline in respiratory function found a 3.0-year delay in the decline of predicted forced vital capacity (FVC) to <60% in nonambulatory patients in Study 019 vs SoC in the CINRG group. The median age for this milestone was 18.1 years in Study 019 and 15.1 years in the CINRG DNHS cohort (P =0.0004).

In the matched populations, 51.1% of patients in Study 019 and 71.1% of patients in the CINRG group experienced a decline to below the 60% predicted FVC threshold. The percentage predicted FVC over time upon losing ambulation indicated a more gradual decline in respiratory function in patients treated with ataluren plus SoC compared with patients receiving SoC alone in the CINRG study.

Results of the study were published in the Journal of Comparative Effectiveness Research.

The authors noted that “the progressive and irreversible effects of DMD underscore the importance of early intervention with treatments that have the potential to slow physical deterioration and delay the natural course of this fatal disease.”


McDonald CM, Munton F, Penematsa V, et al. Ataluren delays loss of ambulation and respiratory decline in nonsense mutation Duchenne muscular dystrophy patients. J Comp Eff Res. Published online November 18, 2021. doi:10.2217/cer-2021-0196