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Nusinersen versus Sham Control in Later-Onset Spinal Muscular Atrophy.
The New England journal of medicine
  • Eugenio Mercuri
  • Basil T Darras
  • Claudia A Chiriboga
  • John W Day
  • Craig Campbell
  • Anne M Connolly
  • Susan T Iannaccone
  • Janbernd Kirschner
  • Nancy L Kuntz
  • Kayoko Saito
  • Perry B Shieh
  • Már Tulinius
  • Elena S Mazzone
  • Jacqueline Montes
  • Kathie M Bishop
  • Qingqing Yang
  • Richard Foster
  • Sarah Gheuens
  • C Frank Bennett
  • Wildon Farwell
  • Eugene Schneider
  • Darryl C De Vivo
  • Richard S Finkel
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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 least-squares 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

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 .).


From New England Journal of Medicine, Mercuri, Eugenio et all, Nusinersen versus Sham Control in Later-Onset Spinal Muscular Atrophy, 378, 625-635 Copyright © 2018 Massachusetts Medical Society. Reprinted with permission.

Citation Information
Eugenio Mercuri, Basil T Darras, Claudia A Chiriboga, John W Day, et al.. "Nusinersen versus Sham Control in Later-Onset Spinal Muscular Atrophy." The New England journal of medicine Vol. 378 Iss. 7 (2018) p. 625 - 635
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