Abstract
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. CLINICALTRIALSGOV 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.
| Original language | English (US) |
|---|---|
| Pages (from-to) | e2492-e2506 |
| Journal | Neurology |
| Volume | 92 |
| Issue number | 21 |
| DOIs | |
| State | Published - May 21 2019 |
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ASJC Scopus subject areas
- Clinical Neurology
Cite this
Nusinersen in later-onset spinal muscular atrophy : Long-term results from the phase 1/2 studies. / ISIS-396443-CS2/ISIS-396443-CS12 Study Groups.
In: Neurology, Vol. 92, No. 21, 21.05.2019, p. e2492-e2506.Research output: Contribution to journal › Article
}
TY - JOUR
T1 - Nusinersen in later-onset spinal muscular atrophy
T2 - Long-term results from the phase 1/2 studies
AU - ISIS-396443-CS2/ISIS-396443-CS12 Study Groups
AU - Darras, Basil T.
AU - Chiriboga, Claudia A.
AU - Iannaccone, Susan T
AU - Swoboda, Kathryn J.
AU - Montes, Jacqueline
AU - Mignon, Laurence
AU - Xia, Shuting
AU - Bennett, C. Frank
AU - Bishop, Kathie M.
AU - Shefner, Jeremy M.
AU - Green, Allison M.
AU - Sun, Peng
AU - Bhan, Ishir
AU - Gheuens, Sarah
AU - Schneider, Eugene
AU - Farwell, Wildon
AU - De Vivo, Darryl C.
PY - 2019/5/21
Y1 - 2019/5/21
N2 - 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. CLINICALTRIALSGOV 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.
AB - 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. CLINICALTRIALSGOV 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.
UR - http://www.scopus.com/inward/record.url?scp=85065524661&partnerID=8YFLogxK
UR - http://www.scopus.com/inward/citedby.url?scp=85065524661&partnerID=8YFLogxK
U2 - 10.1212/WNL.0000000000007527
DO - 10.1212/WNL.0000000000007527
M3 - Article
C2 - 31019106
AN - SCOPUS:85065524661
VL - 92
SP - e2492-e2506
JO - Neurology
JF - Neurology
SN - 0028-3878
IS - 21
ER -