Drisapersen5252. Voit T, Topaloglu H, Straub V, Muntoni F, Deconinck N, Campion G et al. Safety and efficacy of drisapersen for the treatment of Duchenne muscular dystrophy (DEMAND II): an exploratory, randomised, placebo-controlled phase 2 study. Lancet Neurol. 2014;13(10):987-96. https://doi.org/10.1016/S1474-4422(14)70195-4
https://doi.org/10.1016/S1474-4422(14)70...
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2’-O-methyl–Phosphorothioate RNA oligonucleotide that facilitates exon 51 skipping in dystrophin pre-mRNA |
DMD ≥ 5 years; time to rise from floor ≤ 7 s; mutation correctable by skipping exon 51 |
53 patients (18 continuous once a week; 17 intermittent with 9 doses in 10 weeks; 18 placebo) – phase 2 – 48 weeks |
Change in 6MWD at week 25 |
At week 25, 6MWD was higher for continuous treatment (p = 0.014). |
Change in 6MWD at week 49; muscle strength, timed tests, NSAA, dystrophin levels at muscle biopsy |
At week 49 no significant difference was observed between groups. Other secondary endpoints were not statistically different in treated and control groups. |
Eteplirsen5555. Mendell JR, Goemans N, Lowes LP, Alfano LN, Berry K, Shao J et al. Longitudinal effect of eteplirsen versus historical control on ambulation in Duchenne muscular dystrophy. Ann Neurol. 2016;79(2):257-71. https://doi.org/10.1002/ana.24555
https://doi.org/10.1002/ana.24555...
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Phosphorodiamidate morpholino oligomer (PMO); facilitates skipping of exon 51 during pre-mRNA splicing |
DMD with mutations correctable by skipping exon 51 |
12 treated and 13 historical controls – phase 2 – 3 years |
Change in 6MWD |
Slower rate of decline in ambulation (p < 0.01) |
Rate of loss of independent ambulation; relative stability of pulmonary function |
Ataluren5959. Bushby K, Finkel R, Wong B, Barohn R, Campbell C, Comi GP et al. Ataluren treatment of patients with nonsense mutation dystrophinopathy. Muscle Nerve. 2014;50(4):477-87. https://doi.org/10.1002/mus.24332
https://doi.org/10.1002/mus.24332...
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Small molecule that promotes translational read-through of premature stop codons |
DMD patients ≥ 5 years with nonsense point mutation |
174 patients (57 on 40 mg/kg/day; 60 on 80 mg/kg/day; 57 on placebo) – phase 2 – 48 weeks |
Change in 6MWD at week 48 |
Mean decline in 6MWD at week 48: difference of 29.7 m between 40mg/kg/day and placebo (p = 0.149). Difference between 80 mg/kg/day and placebo was negligible. Patients with 6MWD < 350m treated with 40mg/kg/day: 6MWD mean at week 48 was 68.2m better than placebo (p = 0.0053) |
Timed function tests, functional test method grading, at home activity, myometry, patient/caregiver-reported accidental falls, PedsQL physical functioning and psychological domains |
Timed function tests: group 40mg/kg/day trended toward less decline in muscle function compared with placebo. However they met the threshold for clinically meaningful differences. |