Safety and effectiveness of ataluren: comparison of results from the STRIDE Registry and CINRG DMD Natural History Study

Abstract

Aim: Strategic Targeting of Registries and International Database of Excellence (STRIDE) is an ongoing, multicenter registry providing real-world evidence regarding ataluren use in patients with nonsense mutation Duchenne muscular dystrophy (nmDMD). We examined the effectiveness of ataluren + standard of care (SoC) in the registry versus SoC alone in the Cooperative International Neuromuscular Research Group (CINRG) Duchenne Natural History Study (DNHS), DMD genotype–phenotype/–ataluren benefit correlations and ataluren safety. Patients & methods: Propensity score matching was performed to identify STRIDE and CINRG DNHS patients who were comparable in established disease progression predictors (registry cut-off date, 9 July 2018). Results & conclusion: Kaplan–Meier analyses demonstrated that ataluren + SoC significantly delayed age at loss of ambulation and age at worsening performance in timed function tests versus SoC alone (p ≤ 0.05). There were no DMD genotype–phenotype/ataluren benefit correlations. Ataluren was well tolerated. These results indicate that ataluren + SoC delays functional milestones of DMD progression in patients with nmDMD in routine clinical practice. ClinicalTrials.gov identifier: NCT02369731. ClinicalTrials.gov identifier: NCT02369731.

Therapeutic Strategies for Duchenne Muscular Dystrophy: An Update

“…Ataluren (3-(5-(2-fluorophenyl)-(1,2,4]oxa-diazol-3-yl)-benzoic acid), a compound formerly termed as PTC124, also suppresses nonsense mutations with low toxicity [52]. In a phase III trial (NCT01826487), the 6-min walking distance (6MWD) was not significantly improved between treated patients and the placebo group.…”

Nonsense Suppression Therapy: New Hypothesis for the Treatment of Inherited Bone Marrow Failure Syndromes

“…Long-term outcomes of ataluren treatment in DMD patients showed delayed loss of ambulation and prolongation of daily autonomy [199]. As seen elsewhere, ataluren showed a good safety profile, to the extent that ataluren oral administration has been approved in European Union members states also for pediatric DMD patients starting from two years of age [199].…”

“…A study conducted on four non-ambulatory children and adolescents with DMD treated with ataluren demonstrated a mildly attenuated clinical course of the disease, even though a partial reduction of the strength of extensor muscles of the fingers was observed [222]. Long-term outcomes of ataluren treatment in DMD patients showed delayed loss of ambulation and prolongation of daily autonomy [199]. As seen elsewhere, ataluren showed a good safety profile, to the extent that ataluren oral administration has been approved in European Union members states also for pediatric DMD patients starting from two years of age [199].…”

Year in review 2019: Neuromuscular diseases

“…In a study from Mercuri et al 3 the efficacy of ataluren in treating nmDMD was assessed by comparing two populations: patients from the Strategic Targeting of Registries and International Database of Excellence (STRIDE) registry, matched to those from an historical control registry, the Cooperative International Neuromuscular Research Group Duchenne Natural History Study (CINRG DNHS).…”