OBJECTIVES: Estimates of relative treatment effects are required for healthcare decision-making. In the absence of randomized controlled trials (RCTs) with a common comparator for disease-modifying treatments for SMA (gene therapy [onasemnogene abeparvovec], antisense oligonucleotide [nusinersen]), we conducted a matching-adjusted indirect treatment comparison (MAIC).

METHODS: On March 3, 2020, a systematic literature review was conducted to identify evidence for clinical efficacy and safety of currently licensed disease-modifying treatments for SMA1. A Bayesian naïve indirect treatment comparison and MAIC were conducted, using individual patient-level data from onasemnogene abeparvovec trials (START, Cohort 2, N=12; STRIVE-US, N=22) and aggregate data for nusinersen trials (ENDEAR, N=80; SHINE, N=81), to assess relative efficacy and safety. Outcomes: event-free survival (EFS), overall survival (OS), motor milestone achievements (independent sitting, independent walking), and treatment-related adverse events. STR1VE-US 18-month milestone outcomes were carried forward to the 24-month timepoint.

RESULTS: In the base case MAIC analysis (START+STR1VE-US pooled), convergence was reached using both baseline CHOP INTEND score and nutritional support status. Compared to nusinersen, onasemnogene abeparvovec demonstrated a HR of 0.19 (95% CrI, 0.07–0.54) for EFS and 0.35 (95% CrI, 0.09–1.32) for OS. At 24 months of follow-up, subjects receiving onasemnogene abeparvovec were statistically significantly more likely to achieve the motor milestone of sitting independently (RR 2.60, 95% CrI 1.05-6.49). For the motor milestone of independent walking, subjects receiving onasemnogene abeparvovec had a numerically higher likelihood of walking by 24 months of follow-up versus nusinersen (RR 2.08, 95% CrI: 0.06-76.33).

CONCLUSIONS: Despite the methodological challenges due to lack of RCTs with a common comparator and a small sample size (N=34) of the pooled trial arms for onasemnogene abeparvovec, this MAIC indicates that onasemnogene abeparvovec offers significant benefit in terms of OS, EFS, and achievement of sitting or walking independently versus nusinersen up to 24 months of follow-up.