Title

Nusinersen versus Sham Control in Later-Onset Spinal Muscular Atrophy

Authors

Eugenio MercuriFollow
Basil T Darras
Claudia A Chiriboga
John W Day
Craig Campbell, Western UniversityFollow
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

Document Type

Article

Publication Date

2-15-2018

Journal

The New England Journal of Medicine

Volume

378

Issue

7

First Page

625

Last Page

635

URL with Digital Object Identifier

https://doi.org/10.1056/NEJMoa1710504

Abstract

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 ClinicalTrials.gov number, NCT02292537 .).

Notes

Article originally published at The New England Journal of Medicine, Vol. 378(7).

https://doi.org/10.1056/NEJMoa1710504

Copyright © 2018 Massachusetts Medical Society