OBJECTIVES : Patients with infantile-onset spinal muscular atrophy (SMA), a rare, genetic neuromuscular disease, do not achieve key motor function milestones (e.g., sitting) and have short life-expectancy in the absence of treatment. The aim of this study was to estimate the cost-effectiveness of two novel, disease-modifying therapies (nusinersen and onasemnogene abeparvovec) compared to best supportive care (BSC) in patients diagnosed with infantile-onset SMA in the US.

METHODS : A de novo economic model was developed with the following health states: ‘permanent ventilation’, ‘not sitting’, ‘sitting’, ‘walking’, and ‘death’. Short-term data were sourced from the respective pivotal clinical trials of nusinersen (ENDEAR) and onasemnogene abeparvovec (CHERISH). Motor function milestones achieved at the end of follow-up in the clinical trials were assumed to be sustained until death. Mortality risks were based on survival modelling of relevant published Kaplan-Meier data. Costs, life years, and quality-adjusted life years (QALYs) were discounted at 3% per annum, and the analysis was performed from a US health care sector perspective.

RESULTS : For nusinersen, incremental cost effectiveness ratios did not fall below $1 million per QALY gained in scenario and one-way sensitivity analyses accounting for parametric uncertainty. For onasemnogene abeparvovec, at an assumed placeholder price of $2 million, incremental cost-effectiveness ratios ranged from $205,000 to $412,000 per QALY gained. Results were most sensitive to the length of survival, background health care costs, and utility in the ‘sitting’ and ‘walking’ health states.

CONCLUSIONS : The estimated incremental cost-effectiveness of nusinersen and onasemnogene abeparvovec from a US health care sector perspective exceeded commonly-cited cost-effectiveness thresholds of $50,000 to $150,000 per QALY. Cost-effectiveness was dependent on assumptions made about survival, costs, and utilities; and whether the motor function milestones were sustained over lifetime. Given the relatively short-term effectiveness data available for these therapies, a registry to collect long-term data of infantile-onset SMA patients is recommended.