Finkel RS, et al. - This study was performed to compare the effectiveness of nusinersen vs sham control in infantile-onset spinal muscular atrophy. Compared with the control group, infants who received nusinersen were more likely to be alive and have improvements in motor function among infants with spinal muscular atrophy. In order to maximize the benefit of the drug, early treatment could be necessary.

Methods

• A randomized, double-blind, sham-controlled, phase 3 efficacy and safety trial of nusinersen in infants with spinal muscular atrophy was conducted.
• A motor-milestone response (defined according to results on the Hammersmith Infant Neurological Examination) and event-free survival (time to death or the use of permanent assisted ventilation) were the primary end points.
• Overall survival and subgroup analyses of event-free survival according to disease duration at screening were included as secondary end points.
• In a prespecified interim analysis, only the first primary end point was tested.
• A hierarchical testing strategy was used for the second primary end point and the secondary end points in the final analysis to control the overall type I error rate at 0.05.

Results

• In the nusinersen group, a significantly higher percentage of infants than in the control group had a motor-milestone response (21 of 51 infants [41%] vs 0 of 27 [0%], P < 0.001), and this result prompted early termination of the trial in the interim analysis.
• A significantly higher percentage of infants in the nusinersen group than in the control group had a motor-milestone response (37 of 73 infants [51%] vs 0 of 37 [0%]), and the likelihood of event-free survival was higher in the nusinersen group than in the control group (hazard ratio for death or the use of permanent assisted ventilation, 0.53; P=0.005) in the final analysis.
• In the nusinersen group, the likelihood of overall survival was higher than in the control group (hazard ratio for death, 0.37; P=0.004).
• Infants with a shorter disease duration at screening were more likely than those with a longer disease duration to benefit from nusinersen.
• In the 2 groups, the incidence and severity of adverse events were similar.