Risdiplam and nusinersen are disease-modifying therapies (DMTs) approved for treatment of spinal muscular atrophy (SMA). There are no long-term data on relative efficacy and safety of these DMTs. In the absence of head-to-head trials, indirect treatment comparisons adjusted for cross-trial differences can inform treatment decision-making.
To compare long-term efficacy and safety of risdiplam versus nusinersen in children with Type 1 SMA.
Patient-level risdiplam data from 58 children in FIREFISH (Parts 1 and 2; NCT02913482) were compared with published nusinersen data from 81 children in SHINE (ENDEAR cohort; NCT02193074). Matching-adjusted indirect comparisons were used to compare outcomes between risdiplam and nusinersen, adjusting for age at first dose, disease duration and baseline Children’s Hospital of Philadelphia Infant Test of Neuromuscular Disorders (CHOP-INTEND) score. Cox proportional hazards models were used to compare survival, times to Hammersmith Infant Neurological Examination, Module 2 (HINE-2) motor milestone response, CHOP-INTEND response, and any serious adverse event (SAE).
After matching, relevant baseline characteristics were identical across groups. Effective sample size for risdiplam was 40.6. Median follow-up was 3 years (range 2.5–4.5). Compared with the nusinersen group, the risdiplam group had 78% lower rate of death (95% CI 53–96%), 81% lower rate of death or permanent ventilation (95% CI 65–93%), 57% lower rate of SAEs (95% CI 42–68%), and higher rates of HINE-2 and CHOP-INTEND response. While adjustments were made for known prognostic factors, as in any non-randomized comparison, results may be confounded by unobserved baseline differences between groups.
Risdiplam was associated with longer survival, higher rates of motor function responses and lower rates of SAEs than nusinersen in children with Type 1 SMA. This comparative analysis leverages the longest follow-up currently available from two robust clinical trial sources. Additional data sources should be consulted to expand on these findings.