Vamorolone for Duchenne Muscular Dystrophy

Figures

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  Figure 1. Analyzed Cohorts Used in the Cross-Study Comparisons of Vamorolone 6 mg/kg/d, Prednisone 0.75 mg/kg/d, and Deflazacort 0.9 mg/kg/d *Patients had baseline/screening TTSTAND values; however, these were excluded because of the requirement for assistance or incomplete tests. 6MWT = 6-minute walk test; d = day; DMD = Duchenne muscular dystrophy; TTSTAND = time-to-stand from supine; NSAA = North Star Ambulatory Assessment.

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  Figure 2. Forest Plots of Treatment Group Differences Group differences are shown in least-squares mean changes from baseline in time to stand from supine velocity (A), time to run/walk 10-m velocity (B), 6-minute walk test distance (C), and North Star Ambulatory Assessment total score (D) at 6 and 12 months of treatment in the VISION-DMD and FOR-DMD trials using weighted data. Circles represent the least squares mean differences and horizontal lines are 95% CIs. Shaded regions represent the literature-defined minimal clinically important difference thresholds*; if the lower bounds of the 95% CIs for the vamorolone comparisons with prednisone or deflazacort fall below the minimal clinically important difference threshold, one cannot reject the null hypothesis of a clinically important group difference. p Values were not adjusted for multiple testing. *MCID of TTSTAND velocity, 0.023 rises per second27; TTRW velocity, 0.212 m/s27; 6MWT distance, 30 m28; and NSAA total score, 2.32 points.29,30 p Values are derived from the MMRM results shown in detail in Table 2. 6MWT = 6-minute walk test; DFZ = deflazacort 0.9 mg/kg/d; LSM = least squares mean; MCID = minimal clinically important…

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  Figure 3. Changes From Baseline in BMI, Weight, and Height Z-Scores (A) LSM estimates with 95% CI, for comparisons between vamorolone 6.0 mg/kg/d, prednisone 0.75 mg/kg/d, and deflazacort 0.90 mg/kg/d. LSM differences are derived from a weighted MMRM with baseline response, month (weeks 24 and 48 for VISION-DMD and months 6 and 12 for FOR-DMD), treatment, and a treatment-by-visit interaction.* (B) Arithmetic mean changes from baseline with 95% CI. CIs are derived using a t-distribution with n - 1 degrees of freedom where n denotes the number of individuals per treatment and visit. The estimated LSMs in panel A are adjusted for baseline, whereas panel B does not contain such an adjustment. *In panel A, the FOR-DMD population has been reweighted so that the baseline characteristics in key variables match those in VISION-DMD. BMI = body mass index; LSM = least squares mean; MMRM = mixed model for repeated measures; SE = standard error.

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  Figure 4. Vamorolone 2 mg/kg/d vs Intermittent Prednisone 0.75 mg/kg/d (10 Days On/10 Days Off) (A) Forest plots of differences between vamorolone 2 mg/kg/d and intermittent prednisone 0.75 mg/kg/d in least-squares mean changes from baseline. Group differences shown in time to stand from supine velocity, 6-minute walk test distance, time to run/walk 10-m velocity, and North Star Ambulatory Assessment total score at 6 and 12 months of treatment in the VISION-DMD and FOR-DMD trials using weighted data. Circles represent the least squares mean differences, and horizontal lines are 95% CIs. Shaded regions represent the literature-defined minimal clinically important difference thresholds*; if the lower bounds of the 95% CIs for the vamorolone comparisons with prednisone fall below the minimal clinically important difference threshold, one cannot reject the null hypothesis of a clinically important group difference. p Values were not adjusted for multiple testing. (B) Changes in anthropometric values, height, weight, and BMI Z-scores, from baseline. *MCID of TTSTAND velocity, 0.023 rises per second27; TTRW velocity, 0.212 m/s27; 6MWT distance, 30 m28; and NSAA total score, 2.32 points.29,30…