Evaluation of Children with SMA Type 1 Under Treatment with Nusinersen within the Expanded Access Program in Germany

Background: Spinal muscular atrophy (SMA) is a neuromuscular disorder characterized by muscle weakness and muscle atrophy. Nusinersen acts as a splicing modifier and has recently been approved for intrathecal treatment of SMA. Objective: Prior to approval, nusinersen was provided to patients with SMA type 1 in Germany within an Expanded Access Program (EAP). In contrast to previous clinical trials, children of different age groups and different stages of the disease were treated with nusinersen. Methods: We conducted a prospective, longitudinal data collection of patients treated with nusinersen within the EAP in seven neuromuscular centers in Germany. Standardized assessments including CHOP-INTEND and HINE-2 motor milestones were performed at baseline and 60 and 180 days after start of treatment. Results: Data from 61 SMA type 1 patients (mean age 21.08 months, range 1–93) were available for analysis. After six months of treatment, 47 children (77.0%) improved by ≥4 points in CHOP INTEND score. Mean change in CHOP INTEND score was 9.0±8.0 points. Nineteen patients (31.1%) improved by ≥2 points in HINE-2 motor milestones. Regression analysis revealed age at onset of treatment as major determinant of change in CHOP INTEND from baseline. Conclusion: When analyzing a broad spectrum of SMA type 1 patients, many children showed an improvement of motor function after six months of treatment with nusinersen, which is generally not expected within the natural course of the disease. Long-term observation and follow-up of patients with later onset types of SMA are crucial to understand the clinical impact of treatment with nusinersen.