Advancements from the EVOLVE study for assessing real-world experience with eteplirsen, golodirsen and casimersen for the treatment of DMD

Aim: Eteplirsen, golodirsen and casimersen are phosphorodiamidate morpholino oligomers (PMOs) that have received, based on biomarker data, accelerated approval from the US FDA for the treatment of Duchenne muscular dystrophy (DMD) in patients with pathogenic variants amenable to 51, 53 and 45 exon skipping, respectively. The objectives of this study were to describe patient demographic and baseline functional characteristics, safety and treatment continuation in patients with DMD who were treated with a commercially available PMO in the US from the ongoing phase IV, multicenter, prospective, observational EVOLVE study. Patients & methods: Patients who received or initiated treatment with a PMO at the time of study enrollment as prescribed by treating physicians as part of routine care were included. Approximately 300 patients will be enrolled across the three PMOs. Results: As of this 2023 interim data report, 161 patients were enrolled: 126 were treated with eteplirsen (enrollment complete), mean (standard deviation [SD]) age 14.0 (5.51) years; 23 received golodirsen, mean (SD) age 13.3 (4.25) years; and 12 were treated with casimersen, mean (SD) age 16.1 (7.21) years. Mean (SD) total duration of treatment was 6.2 (1.92) years for eteplirsen, 2.4 (0.83) years for golodirsen and 1.7 (0.62) years for casimersen. All PMOs demonstrated favorable safety profiles, with no treatment-emergent serious adverse events related to treatment. Most patients taking eteplirsen (95.2%, n = 120) continued treatment. Among the 85 patients who were ambulatory at treatment initiation, 37 patients lost ambulation, 34 (91.9%) of whom remained on eteplirsen. Conclusion: Consistent with the safety findings from previous clinical trials, eteplirsen, golodirsen and casimersen showed favorable safety profiles in patients with DMD in routine clinical practice. EVOLVE will continue to describe long-term clinical outcomes Clinical Trial Registration Number: NCT06606340.