Background
Spinal muscular atrophy (SMA) is a genetic, progressive neuromuscular disease characterized by motor neuron loss. Risdiplam (EVRYSDI®), the only orally administered survival of motor neuron 2 (SMN2) pre-mRNA splicing modifier, is an FDA-approved treatment for pediatric and adult individuals with SMA.
Objective
This Phase 4, multi-center, longitudinal, prospective, non-comparative study (WeSMA; NCT05232929) will investigate risdiplam’s long-term safety and effectiveness in individuals with all SMA types.
Methods
Individuals with SMA who are receiving risdiplam as part of their clinical care are eligible. Exclusion criteria include risdiplam hypersensitivity or participation in another risdiplam trial. Enrollment of up to 500 individuals is planned. Follow-up is up to 5 years from enrollment or until consent withdrawal, loss to follow-up or death. Primary outcomes are adverse event (AE) rates, AEs of special interest and serious AEs. The secondary outcome is the percentage of participants improved on the Clinical Global Impression-Change scale
(CGI-C). Exploratory outcomes are changes over time in motor, respiratory and bulbar functions; hospitalizations; survival in infants aged <2 years with Type 1 SMA; and patient- and caregiver-reported outcomes.
Results
Ninety-seven individuals are included in this baseline analysis (data cut-off: July 17, 2023). Mean (SD) age at study enrollment was 22.5 (17.0) years, and mean (SD) age at diagnosis was 4.7 (9.7) years. Most (n=46 [56.1%]) had 3 SMN2 copies. Over half (n=67 [69.1%]) were established on risdiplam (i.e. >6 months at study enrollment) with a mean (SD) risdiplam duration of 20.1 (6.4) months. Eleven (11.3%) individuals were newly prescribed risdiplam (i.e. ≤6 months of use), with a mean (SD) risdiplam duration of 1.4 (1.8) months. Sixty (61.9%) individuals previously received another SMA disease-modifying therapy.
Conclusions
WeSMA will provide data on risdiplam’s real-world use, safety and effectiveness in a broad population of individuals with SMA.