Nusinersen versus sham control in later-onset spinal muscular atrophy

Eugenio Maria Mercuri, Marco Piastra, Elena Stacy Mazzone, Elisabeth Margarete Ute Schneider-Moser, Maria Carmela Pera, B. T. Darras, C. A. Chiriboga, J. W. Day, C. Campbell, A. M. Connolly, S. T. Iannaccone, J. Kirschner, N. L. Kuntz, K. Saito, P. B. Shieh, M. Tulinius, J. Montes, K. M. Bishop, Q. Yang, R. FosterS. Gheuens, C. F. Bennett, W. Farwell, E. Schneider, D. C. De Vivo, R. S. Finkel

Risultato della ricerca: Contributo in rivistaArticolo in rivista

465 Citazioni (Scopus)


BACKGROUND: Nusinersen is an antisense oligonucleotide drug that modulates pre-messenger RNA splicing of the survival motor neuron 2 (SMN2) gene. It has been developed for the treatment of spinal muscular atrophy (SMA). METHODS: We conducted a multicenter, double-blind, sham-controlled, phase 3 trial of nusinersen in 126 children with SMA who had symptom onset after 6 months of age. The children were randomly assigned, in a 2:1 ratio, to undergo intrathecal administration of nusinersen at a dose of 12 mg (nusinersen group) or a sham procedure (control group) on days 1, 29, 85, and 274. The primary end point was the leastsquares mean change from baseline in the Hammersmith Functional Motor Scale-Expanded (HFMSE) score at 15 months of treatment; HFMSE scores range from 0 to 66, with higher scores indicating better motor function. Secondary end points included the percentage of children with a clinically meaningful increase from baseline in the HFMSE score (≥3 points), an outcome that indicates improvement in at least two motor skills. RESULTS: In the prespecified interim analysis, there was a least-squares mean increase from baseline to month 15 in the HFMSE score in the nusinersen group (by 4.0 points) and a least-squares mean decrease in the control group (by -1.9 points), with a significant between-group difference favoring nusinersen (least-squares mean difference in change, 5.9 points; 95% confidence interval, 3.7 to 8.1; P<0.001). This result prompted early termination of the trial. Results of the final analysis were consistent with results of the interim analysis. In the final analysis, 57% of the children in the nusinersen group as compared with 26% in the control group had an increase from baseline to month 15 in the HFMSE score of at least 3 points (P<0.001), and the overall incidence of adverse events was similar in the nusinersen group and the control group (93% and 100%, respectively). CONCLUSIONS: Among children with later-onset SMA, those who received nusinersen had significant and clinically meaningful improvement in motor function as compared with those in the control group. (Funded by Biogen and Ionis Pharmaceuticals; CHERISH number, NCT02292537).
Lingua originaleEnglish
pagine (da-a)625-635
Numero di pagine11
RivistaNew England Journal of Medicine
Stato di pubblicazionePubblicato - 2018


  • Age of Onset
  • Child
  • Child, Preschool
  • Double-Blind Method
  • Female
  • Humans
  • Infant
  • Injections, Spinal
  • Least-Squares Analysis
  • Male
  • Medicine (all)
  • Motor Skills
  • Oligonucleotides
  • Oligonucleotides, Antisense
  • Spinal Muscular Atrophies of Childhood


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