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Tofersen Treatment in SOD1-ALS: Real-World Evidence from a Retrospective Multicenter Study in France (FORSLA Study)
Daniells Erazo1,2,3, Adele Hesters1,4, Gaëlle Bruneteau1,4,5,6
1FILSLAN - French rare disease healthcare network, France.
Mayo Clinic Proceedings. Innovations, Quality & Outcomes
|August 4, 2026
Summary
Tofersen treatment in SOD1-ALS patients demonstrated a significant slowing of disease progression and reduction in neurofilament light chain levels in a real-world French setting. These findings suggest Tofersen offers a clinical benefit for managing SOD1-ALS.
Area of Science:
- Neurology
- Genetics
- Pharmacology
Background:
- Amyotrophic Lateral Sclerosis (ALS) is a progressive neurodegenerative disease.
- Superoxide Dismutase 1 (SOD1) gene mutations are a cause of familial ALS.
- Tofersen is an investigational therapy targeting SOD1 mutations.
Purpose of the Study:
- To evaluate the real-world effectiveness of Tofersen in SOD1-ALS patients in France.
- To assess Tofersen's impact on disease progression and biomarkers.
Main Methods:
- A real-world cohort study involving 46 SOD1-ALS patients treated with Tofersen across 19 French centers.
- Comparison of disease progression (ALSFRS-R) and neurofilament light chain (NfL) levels within the Tofersen cohort.
- Exploratory comparison with a propensity score-matched historical cohort.
Main Results:
- Tofersen treatment significantly slowed ALSFRS-R progression (0.53 to 0.22 points/month) and reduced NfL levels (89.0 to 29.2 pg/ml) within 12 months.
- No significant difference in ALSFRS-R progression rate between Tofersen and historical cohorts at 12 months.
- Longitudinal ALSFRS-R scores differed significantly, and Tofersen cohort showed longer survival (42.6 vs 31.8 months) with reduced mortality risk (HR=0.34).
Conclusions:
- Tofersen appears to slow functional decline and lower NfL levels in SOD1-ALS patients in a real-world setting.
- Findings suggest a potential clinical benefit of Tofersen, despite limitations of the retrospective design.
- Real-world data supports Tofersen's efficacy in managing SOD1-ALS progression and mortality.
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