G.P.113: Drisapersen (DRIS) treatment for Duchenne muscular dystrophy (DMD): Results of up to 188 weeks’ follow-up of an open-label extension study

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Drisapersen (DRIS) is a 2’-O-methyl-phosphorothioate antisense oligonucleotide that induces skipping of exon 51 to correct Duchenne muscular dystrophy (DMD) mutations. This open-label extension (OLE) to a 5-week dose-escalation study assessed the long-term safety and efficacy of 6 mg/kg DRIS in 12 boys (5–16 years) with DRIS-correctable mutations. Dosing was once weekly for 72 weeks, with a planned interruption (weeks 73–80), followed by intermittent dosing (Weeks 81–188). Median (mean [SD]) 6-min walking distance (6MWD) declined between original baseline and OLE baseline (6–15 months) from 394 (402 [73]) to 362 (384 [121]) m at OLE baseline (n = 10). At Week 177, the mean (range) age of boys who completed the 6MWD at OLE baseline (n = 10) was 12.9 (9.3–15.4) years. The median (mean [SD]) change from OLE baseline was +7.5 (−24.5 [161]) m for these 10 boys; 2 boys (baseline 6MWD 140 m further than at OLE baseline. The mean (SD) change from OLE baseline to Week 177 in rise from floor was 1.0 (0.9) s for boys (n = 6) who attempted the test, and 6.9 (10.7) s when missing data for boys unable to attempt the test were replaced by 30s (n = 11). There was a mean (SD) change from OLE baseline to Week 177 in absolute forced vital capacity of 0.06 (0.29) L (n = 12). There were no clear trends in other timed tests. Over 188 weeks, all 12 boys had ⩾1 adverse event (study drug-related injection-site reactions, n = 12; gastrointestinal disorders, n = 6; decreased platelet counts, n = 5). All had increases in urine α-1-microglobulin levels and transient mild proteinuria; these were non-progressive and reversible in drug-free periods. No boys permanently withdrew from treatment. Data from this OLE are encouraging, as the natural history of DMD in steroid-treated boys receiving standard care at one of the study sites shows a median (mean [SD]) 6MWD decline of −106 (−125 [139])m over 104 weeks.