Later-Onset Spinal Muscular Atrophy Benefits From Nusinersen

cerebrospinal fluid csf
cerebrospinal fluid csf
Improved motor function was observed among more participants in the nusinersen group compared with those in the control group.

Children with later-onset spinal muscular atrophy (SMA) who are treated with nusinersen experience significant, clinically meaningful improvements in motor function compared with those who receive a sham procedure, according to the results of the multicenter, double-blind, sham-controlled, phase 3 CHERISH study (ClinicalTrials.gov identifier: NCT02292537) published in The New England Journal of Medicine.

The study included 126 children with SMA (symptom onset >6 months of age). All participants were randomly assigned, in a 2:1 ratio, to receive intrathecal administration of nusinersen 12 mg or a sham procedure on days 1, 29, 85, and 274 (maintenance dose). The sham procedure, which was performed on the same 4 days, involved a small needle prick on the lower back that was covered with a bandage to resemble a lumbar puncture.

The primary end point of the study was the least-squares mean change from baseline in the Hammersmith Functional Motor Scale-Expanded (HFMSE) score at 15 months of treatment. The HFMSE scores range from 0 to 66, with higher scores denoting better motor function. Secondary end points included the percentage of participants with a clinically meaningful increase from baseline in HFMSE score (≥3 points), which is indicative of improvement in ≥2 motor skills.

Findings from the prespecified interim analysis showed a least-squares mean increase of 4.0 points from baseline to 15 months in HFMSE scores in the nusinersen group compared with a least-squares mean decrease of 1.9 points in HFMSE score in the control group. A significant between-group difference in favor of nusinersen was reported (least-squares mean difference in change of 5.9 points; 95% CI, 3.7-8.1; P <.001), which resulted in early trial termination. 

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Results of the final analysis were consistent with those from the interim analysis. In the final analysis, 57% of children in the nusinersen arm and 26% of those in the control arm had an increase in HFMSE score of ≥3 points from baseline to month 15 (P <.001). The overall incidence of any adverse events was similar in the nusinersen group (93%) and the control group (100%).

The investigators concluded that nusinersen therapy in children with later-onset SMA is associated with positive outcomes, including improved motor function.

Reference

Mercuri E, Darras BT, Chiriboga CA, et al; CHERISH Study Group. Nusinersen versus sham control in later-onset spinal muscular atrophy. N Engl J Med. 2018;378(7):625-635.