Disease-modifying therapies for spinal muscular atrophy improved or stabilized motor and respiratory outcomes in real-world settings, though high costs frequently resulted in ICERs above standard thresholds.
Systematic Review (n=159)
Do EMA-approved orphan medicines for spinal muscular atrophy improve clinical outcomes and demonstrate cost-effectiveness in real-world practice?
Real-world evidence confirms that disease-modifying therapies for SMA improve or stabilize clinical outcomes, especially when initiated early, but their high acquisition costs pose significant challenges to cost-effectiveness.
Background : Spinal muscular atrophy (SMA) is a rare neuromuscular disorder associated with a substantial clinical burden, high supportive-care needs, and a major economic impact. The introduction of disease-modifying therapies (DMTs) has transformed the management of SMA, but questions remain regarding their real-world effectiveness and economic value. Objective : To conduct a systematic literature review of published studies on the real-world effectiveness and economic evaluations of orphan medicines for spinal muscular atrophy approved within the European Union. Materials and methods : A systematic literature review was conducted according to a prespecified protocol registered in the Open Science Framework and reported in line with PRISMA 2020 and Joanna Briggs Institute methodologies. PubMed, Embase, Web of Science, and Google Scholar were searched between 16 and 30 May 2025 without date restrictions. Two review components were assessed under one protocol: (1) real-world clinical evidence for approved SMA therapies and (2) economic evaluations of these therapies. After screening and full-text review, 114 real-world evidence (RWE) studies and 19 economic studies met the eligibility criteria; an additional 16 RWE studies and 10 economic studies were identified from gray literature. Results : A total of 159 studies were included. Across real-world studies, nusinersen, risdiplam, and onasemnogene abeparvovec were generally associated with improved or stabilized outcomes, particularly for motor and respiratory function. The greatest benefits were observed with presymptomatic or very early treatment initiation, whereas in later-treated children and adults, stabilization and slowing of decline were often the most clinically meaningful outcomes. Bulbar and feeding outcomes remained less consistently improved and were reported heterogeneously. Survival outcomes were generally favorable in short- to medium-term follow-up. Economic evaluations consistently showed that treatment cost was the main driver of cost-effectiveness. Most analyses reported incremental cost-effectiveness ratios above conventional willingness-to-pay thresholds, although onasemnogene abeparvovec and presymptomatic treatment scenarios often appeared more favorable. Considerable uncertainty remains regarding the long-term durability of benefit and model assumptions. Conclusion : In routine practice, DMTs for SMA improve or stabilize important clinical outcomes, with the strongest effects seen when treatment is started early. However, high acquisition costs and limited long-term data continue to challenge cost-effectiveness. More standardized, long-term real-world evidence is needed to strengthen clinical guidance, improve economic models, and support sustainable access decisions.
Boseva-Stoyanova et al. (Thu,) conducted a systematic review in Spinal muscular atrophy (SMA) (n=159). EMA-approved orphan medicines (nusinersen, risdiplam, onasemnogene abeparvovec) vs. Other EMA-approved orphan drugs or standard of care was evaluated on Real-world effectiveness (motor, respiratory, feeding, survival) and cost-effectiveness outcomes. Disease-modifying therapies for spinal muscular atrophy improved or stabilized motor and respiratory outcomes in real-world settings, though high costs frequently resulted in ICERs above standard thresholds.