Cardiac Safety Outcomes in Delandistrogene Moxeparvovec Clinical Trials for Duchenne Muscular Dystrophy with Up to 5 Years of Follow-up

Figures

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  Fig. 1. Troponin I fluctuations in individual participants in a EMBARK, parts 1 and 2 (n = 93)a,b and b ENDEAVOR, cohorts 1–5 (n = 46).a aEach line corresponds to the troponin I levels from a single participant. For clarity, data from patients with troponin I values > 1.3 µg/L are omitted from the enlarged image. Since normal levels of troponin I in patients with DMD have not been established, the upper limit of troponin I used in both EMBARK and ENDEAVOR (0.058 µg/L) was based on observed values. bEMBARK was a crossover trial, in which patients were randomized 1:1 to receive delandistrogene moxeparvovec or placebo infusion at the beginning of a 52-week part 1. The treatment assignment was switched at the beginning of a 52-week part 2. Dotted lines indicate participants with more than one elevated troponin I value. DMD Duchenne muscular dystrophy, ULN upper limit of normal

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  Fig. 2. a–d Measures of left ventricular function, volume, and mass over time: EMBARK cMRI substudy (n = 39).a aPoint estimates at the end of part 1 (week 52) were very similar but not identical to the point estimates for the baseline of part 2. For clarity, only baseline part 2 values are shown. bNumbers of patients at visits indicate those with ECHO LVEF data available both at baseline and at that visit. cMRI cardiac magnetic resonance imaging, LV left ventricle, LVEF left ventricular ejection fraction

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  Fig. 3. Change in LVEF (by ECHO) over timea in a study 102 (n = 41),b b ENDEAVOR cohorts 2, 3, and 5bc (n = 15), and c EMBARK (n = 125). aNumbers of patients at visits indicate those with ECHO LVEF data available both at baseline and at that visit. bIn study 102, parts 1 and 2 were 48 weeks in duration each. In phase 2, participants received the double-blinded infusion at variable times following the completion of 48 weeks of phase 1. In this graph, for simplicity, phase 1 LVEF values at week 48 were considered to be identical to the values obtained 1 day before the phase 2 infusion. For the same reason, week 4 data for both phase 1 and phase 2 are not shown. cFor clarity, only ENDEAVOR cohorts 2, 3, and 5b are shown here, because they include late-ambulatory or non-ambulatory patients (Table 1), in whom cardiac issues would be expected. Patients with LVEF < 50% at any visit are indicated in red, purple, or blue color. The bar chart was used to enhance presentation of individual data. ECHO echocardiogram, LVEF left ventricular ejection fraction