Presentation (CTI)

OBJECTIVES: Duchenne muscular dystrophy (DMD) is a rare neuromuscular disease caused by pathogenic variants in the DMD gene and characterized by childhood-onset muscle weakness, with progressive functional decline. Eteplirsen, golodirsen, and casimersen are phosphorodiamidate morpholino oligomers (PMOs) indicated for treating patients with DMD amenable to skipping exons 51, 53, and 45, respectively. This study aimed to synthesize evidence on functional outcomes and survival among individuals with DMD treated with these PMOs.
METHODS: A systematic review was conducted to identify clinical trials and observational studies evaluating PMOs (timeframe: 2012-2025). Outcomes of interest were descriptively summarized, comprising measures of ambulatory, respiratory, cardiac function, and survival. The analysis was limited to efficacy/effectiveness data; safety was excluded.
RESULTS: From 1,964 abstracts screened, 18 publications of 10 interventional and observational studies described outcomes following eteplirsen, golodirsen, or casimersen treatment; the evidence base for eteplirsen was most robust (seven studies). In pooled analyses, median age at loss of ambulation (LOA) for eteplirsen-treated patients was significantly later than natural history controls (15.7 vs 13.0 years, p=0.03); similar benefits were observed from post-hoc analyses of golodirsen vs matched controls (median time to LOA: 6 vs 3.1 years, respectively, p=0.0016). Eteplirsen-treated patients had a significant attenuation in percent predicted forced vital capacity (FVC%p) decline vs natural history controls (2.2% vs 6.0%, respectively; p<0.001), as did golodirsen-treated (2.9% vs 6.7%; p<0.01) and casimersen-treated patients (5.5% vs 8.2%; p<0.01). Cardiac outcome and survival data were available for eteplirsen only; evidence indicated slower left ventricular ejection fraction decline and lower hazard of death (crude hazard ratio: 0.34 [95% confidence interval: 0.23-0.50]) among eteplirsen-treated patients than natural history controls.
CONCLUSIONS: This review revealed a larger evidence base for the efficacy/effectiveness of eteplirsen among PMOs, driven by its longer period of commercial availability. Emerging data for golodirsen and casimersen observed similar trends.