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Nusinersen in later-onset spinal muscular atrophy
17 auth. B. Darras, C. Chiriboga, S. Iannaccone, K. Swoboda, J. Montes, L. Mignon, S. Xia, C. Bennett, K. Bishop, J. Shefner, ...
Objective To report results of intrathecal nusinersen in children with later-onset spinal muscular atrophy (SMA). Methods Analyses included children from a phase 1b/2a study (ISIS-396443-CS2; NCT01703988) who first received nusinersen during that st…
Objective To report results of intrathecal nusinersen in children with later-onset spinal muscular atrophy (SMA). Methods Analyses included children from a phase 1b/2a study (ISIS-396443-CS2; NCT01703988) who first received nusinersen during that study and were eligible to continue treatment in the extension study (ISIS-396443-CS12; NCT02052791). The phase 1b/2a study was a 253-day, ascending dose (3, 6, 9, 12 mg), multiple-dose, open-label, multicenter study that enrolled children with SMA aged 2–15 years. The extension study was a 715-day, single-dose level (12 mg) study. Time between studies varied by participant (196–413 days). Assessments included the Hammersmith Functional Motor Scale–Expanded (HFMSE), Upper Limb Module (ULM), 6-Minute Walk Test (6MWT), compound muscle action potential (CMAP), and quantitative multipoint incremental motor unit number estimation. Safety also was assessed. Results Twenty-eight children were included (SMA type II, n = 11; SMA type III, n = 17). Mean HFMSE scores, ULM scores, and 6MWT distances improved by the day 1,150 visit (HFMSE: SMA type II, +10.8 points; SMA type III, +1.8 points; ULM: SMA type II, +4.0 points; 6MWT: SMA type III, +92.0 meters). Mean CMAP values remained relatively stable. No children discontinued treatment due to adverse events. Conclusions Nusinersen treatment over ∼3 years resulted in motor function improvements and disease activity stabilization not observed in natural history cohorts. These results document the long-term benefit of nusinersen in later-onset SMA, including SMA type III. Clinicaltrials.gov identifier NCT01703988 (ISIS-396443-CS2); NCT02052791 (ISIS-396443-CS12). Classification of evidence This study provides Class IV evidence that nusinersen improves motor function in children with later-onset SMA.
Published in
Neurology
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34
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7 | 2019 |
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