Supplementary materials: Confirmatory long-term efficacy and safety results of ataluren in patients with nmDMD from Study 041, an international, randomized, double-blind, placebo-controlled, phase III trial

<b>These are peer-reviewed supplementary materials for the article</b><b> '</b><b>Confirmatory long-term efficacy and safety </b><b>results of ataluren in patients with </b><b>nmDMD from Study 041, an international, </b><b>randomized, double-blind, </b><b>placebo-controlled, phase III trial</b><b>'</b><b> </b><b>published in the</b><b> </b><b><i>Journal of Comparative Effectiveness Research</i></b><b>.</b><b>Supplementary appendix</b><b>Supplementary figure 1</b><b>Supplementary figure 2</b><b>Supplementary figure 3</b><b>Supplementary figure 4</b><b>Supplementary figure 5</b><b>Supplementary table 1:</b> Patients enrolled in Study 041 by country<b>Supplementary table 2:</b> Study 041 analysis populations<b>Supplementary table 3:</b> TEAEs reported for ≥ 5% of patients who received ataluren or placebo in the as-treated population<b>Supplementary table 4:</b> Corticosteroid use and baseline time to stand from supine of &lt; 5 seconds for patients who lost ambulation at week 72 in the ITT population<b>Supplementary table 5:</b> Time to LoA at week 48 in the ITT population and key subgroups<b>Supplementary table 6:</b> Time to a 5% persistent worsening and a 30 m decline in 6MWD in the ITT population and the 6MWD 300–400 m subgroup<b>Supplementary table 7:</b> Changes in PUL module scores from baseline to week 72 in the Study 041 ITT population and the 6MWD 300–400 m subgroup<b>Aim:</b> To report the efficacy and safety of ataluren in patients with nonsense mutation Duchenne muscular dystrophy (nmDMD) from the phase III, 72-week, placebo-controlled period of Study 041. <b>Materials </b><b>&amp; methods:</b> Inclusion criteria: boys with nmDMD aged ≥5 years, on a stable corticosteroid regimen for ≥12 months, and baseline 6-minute walk distance (6MWD) ≥150 m. Randomization: 1:1, ataluren (40 mg/kg/day):placebo. Primary end point: slope of 6MWD change (average rate of change). Secondary end points: changes in 6MWD, time to 10% persistent worsening in 6MWD, North Star Ambulatory Assessment score, timed function tests and safety. Study populations: intention-to-treat; patients aged ≥7 to ≤16 years with baseline 6MWD ≥300 m and stand from supine ≥5 s; patients with baseline 6MWD 300–400 m.<b> Results:</b> In the intention-to-treat population (n = 359), over 72 weeks, ataluren reduced the rate of 6MWD decline by 21% (p = 0.0248), reduced the average 6MWD change (p = 0.0248), delayed time to 10% persistent worsening in 6MWD (p = 0.0078), and reduced North Star Ambulatory Assessment total score decline (p = 0.0235), change in 10 m walk/run time (p = 0.0422) and change in time to climb four stairs (p = 0.0293) versus placebo. In the 6MWD 300–400 m subgroup (n = 169), ataluren reduced the rate of 6MWD decline by 30% (p = 0.0310) versus placebo. Ataluren treatment benefits were seen in secondary end points in this subgroup, except for change in time to descend four stairs. In the 6MWD ≥300 m and time to stand from supine ≥5s subgroup (n = 185), there was a 9% slower rate of 6MWD decline for ataluren versus placebo over 72 weeks (p = 0.3626). Ataluren reduced change in time to climb four stairs (p = 0.0179) versus placebo in this subgroup; no treatment benefits were seen for other secondary end points. Ataluren was well tolerated (serious adverse events: ataluren, 7.1%; placebo, 6.8%); no deaths occurred. <b>Conclusion:</b> Long-term ataluren treatment has a favorable benefit–risk profile, slowing motor function decline in the largest phase III nmDMD study to date.