OBJECTIVES: To conduct an updated matching-adjusted indirect comparison (MAIC) to evaluate relative efficacy and safety of risdiplam versus nusinersen in Type 1 spinal muscular atrophy (SMA) using latest available data.

METHODS: Pooled 2-year risdiplam data from 58 infants in FIREFISH Part 1 (NCT02913482; n=17; pivotal-dose cohort) and Part 2 (n=41) were compared with nusinersen data from 81 patients in the SHINE/ENDEAR cohort (NCT02193074). MAIC was used to compare individual patient-level risdiplam data with aggregated nusinersen data extracted from publicly available sources. Populations were matched using previously identified prognostic factors and effect modifiers in Type 1 SMA: age at first dose, symptom duration and Children’s Hospital of Philadelphia Infant Test of Neuromuscular Disorders (CHOP-INTEND) score. Comparisons were conducted on time‑to‑event outcomes; hazard ratios (HRs) of risdiplam versus nusinersen were estimated using Cox proportional-hazards models.

RESULTS: FIREFISH and the SHINE/ENDEAR cohort enrolled populations with comparable baseline characteristics. The effective sample size for risdiplam after matching was 36.5. MAIC suggests that patients treated with risdiplam may be 81% less likely to die (overall survival HR 0.19; 95% confidence interval [CI] 0.02–0.54) and 81% less likely to die or require permanent ventilation (event-free survival HR 0.19; 95% CI 0.07–0.39) compared with patients who received nusinersen. Risdiplam treatment may also reduce the likelihood of experiencing a serious adverse event (SAE) and may result in a higher likelihood of functional improvement (assessed by the Hammersmith Infant Neurological Exam, Module 2 [HINE-2]) or earlier functional improvement (assessed by CHOP-INTEND) compared with nusinersen treatment. Unadjusted indirect comparison analyses yielded similar results. These results are consistent with previously published 12-month findings.

CONCLUSIONS: Updated MAIC results from the FIREFISH and SHINE/ENDEAR studies suggest that in patients with Type 1 SMA, risdiplam may yield better results on multiple outcomes compared with nusinersen over 24 months of follow-up.