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.
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.
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.