Long-Term Comparative Efficacy and Safety of Risdiplam versus Nusinersen in Children with Type 1 Spinal Muscular Atrophy (SMA)

Background/Purpose: Risdiplam (EVRYSDI) and nusinersen (SPINRAZA) are approved disease-modifying therapies (DMTs) for 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. This study compared long-term efficacy and safety of risdiplam versus nusinersen in children with Type 1 SMA.

Methods: Patient-level risdiplam data from 58 children in FIREFISH (Parts 1 and 2; NCT02913482) and published nusinersen data from 81 children in SHINE (ENDEAR cohort; NCT02193074) were compared. Matching-adjusted indirect comparisons (MAICs) were conducted, 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 and times to Hammersmith Infant Neurological Examination, Module 2 (HINE-2) and CHOP-INTEND responses, and time to first serious adverse event (SAE).

Results: 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 nusinersen, risdiplam led to reductions of 78% in the rate of death, 81% in the rate of death or permanent ventilation and 57% in the rate of SAEs, and increases of 45 and 189% in the rate of achieving HINE-2 and CHOP-INTEND responses, respectively. While adjustments were made for known prognostic factors, as with any non-randomized comparison, results may be confounded by unobserved baseline differences between groups.

Conclusion: MAIC suggested that children with Type 1 SMA treated with risdiplam may experience greater improvements in survival, motor function, and time to first SAE compared with nusinersen. These analyses leveraged the longest follow-up available from FIREFISH and SHINE. Additional data sources should be consulted to expand on these findings.

Publication History

Article published online:
13 November 2023