Eteplirsen, golodirsen, and casimersen are exon-skipping therapies approved for patients with Duchenne muscular dystrophy (DMD) with mutations amenable to 51, 53, and 45 exon skipping, respectively. An ongoing 5-year, phase 4, multicenter, observational study is assessing the safety, usage, and clinical outcomes of their long-term use in routine clinical practice.
This interim analysis includes data on serious adverse events (SAEs) and adverse events of special interest, as well as loss of ambulation (LOA).
As of December 2021, 144 patients were enrolled with a mean (SD) age (years) of: eteplirsen (n=123), 13.7 (5.5); golodirsen (n=17), 13.5 (4.3); and casimersen (n=4), 16.3 (11.7). Mean (SD) duration of treatment (years) was 4.7 (1.88) for eteplirsen, 1.3 (0.45) for golodirsen, and 0.3 (0.22) for casimersen. Mean time (years) from DMD diagnosis to treatment initiation was: eteplirsen, 6.0 (4.74); golodirsen 8.2 (3.76); and casimersen 13.5 (14.04). At treatment initiation, 82/123 (66.7%) eteplirsen-treated, 7/17 (41.2%) golodirsen-treated, and 2/4 (50%) casimersen-treated patients were ambulatory. To date, favorable safety profiles have been observed for all 3 therapies. During EVOLVE, SAEs occurred in 14 (11.4%) eteplirsen-treated patients, consistent with the known safety profile of eteplirsen; none were reported for golodirsen or casimersen. Median age at LOA for eteplirsen-treated patients is 15.3 years, consistent with prior clinical trial post hoc results; small sample size to date precludes analysis of age at LOA for golodirsen or casimersen.
These real-world data from the interim analysis of EVOLVE support the safety profiles and will continue to describe long-term clinical outcomes of eteplirsen, golodirsen, and casimersen.