Tofersen Treatment in SOD1-ALS: Real-World Evidence from a Retrospective Multicenter Study in France (FORSLA Study)

Objective To evaluate the effectiveness of Tofersen in patients with superoxide dismutase 1 gene ( SOD1-ALS ) patients in France in a real-world setting, using disease progression within patient comparisons and with a historical cohort. Patients and Methods Patients with SOD1 -ALS were included from across 19 French FILSLAN network centers. Baseline was defined as the treatment initiation date. Main endpoints were the ALSFRS-R progression rate and plasmatic neurofilament light chain (NfL) levels at baseline and 12 months after baseline. Results In the Tofersen Cohort (N=46), within-group comparisons showed that the mean ALS functional rating scale revised (ALSFRS-R) progression rate slowed from 0.53 ± 0.5 at baseline to 0.22 ± 0.3 point/month at 12 months ( P =.006). NfL levels significantly decreased from 89.0 ± 9.0 pg/ml at baseline to 29.2 ± 19.5.5 at 12 months ( P =.004). Exploratory comparisons with a propensity score (PS) matched historical cohort (39 matched pairs) using a mixed-effects model, ALSFRS-R progression rate at baseline, 6 months, and 12 months after baseline, showed no statistically significant differences between groups P =.30, whereas longitudinal ALSFRS-R scores differed significantly between groups (time-treatment interaction P =.006). The mean survival of the PS matched population was longer in the Tofersen Cohort (42.6 months) than the Historical Cohort (31.8 months) P =.004. Time-dependent adjusted cox analysis showed that Tofersen was associated with a reduction in mortality risk (adjusted HR=0.34; 95% CI, 0.12-0.91; P =.03). Conclusion Tofersen seems to be associated with slower functional decline and reduced NfL levels. While limitations of retrospective design and ALSFRS-R sensitivity must be acknowledged, these findings provide real-world evidence suggesting a clinical benefit of Tofersen.

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Journal
Mayo Clinic Proceedings Innovations Quality & Outcomes
Published
2026-07-27
DOI
https://doi.org/10.1016/j.mayocpiqo.2026.100739
Primary Topic
Amyotrophic Lateral Sclerosis Research
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article
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article

Tofersen Treatment in SOD1-ALS: Real-World Evidence from a Retrospective Multicenter Study in France (FORSLA Study)

Marie Templé, Claire Guissart, Nathalie Guy, Elisa De la Cruz et al.
Mayo Clinic Proceedings Innovations Quality & Outcomes
Amyotrophic Lateral Sclerosis Research
article

Tofersen Treatment in SOD1-ALS: Real-World Evidence from a Retrospective Multicenter Study in France (FORSLA Study)

Marie Templé, Claire Guissart, Nathalie Guy, Elisa De la Cruz, Mathilde Lefilliatre, Steeve Genestet, Daniells Erazo, Gwendal Le Masson, Aude‐Marie Grapperon, Véronique Danel, Philippe Couratier, Kévin Mouzat, Agnès Jacquin, Shahram Attarian, Pascal Cintas, Adrien Bohic, Florence Esselin, Géraldine Lautrette, Julie Catteau, Sophie Pittion, Marie‐Claire Vincent, Adèle Hesters, Ariane Choumert, E Bernard, Julien Cassereau, François Salachas, Philippe Corcia, Jean-Philippe Camdessanché, Patrick Vourc’h, Gaëlle Bruneteau, Marie-Hélène Soriani
article en

Abstract

Objective To evaluate the effectiveness of Tofersen in patients with superoxide dismutase 1 gene ( SOD1-ALS ) patients in France in a real-world setting, using disease progression within patient comparisons and with a historical cohort. Patients and Methods Patients with SOD1 -ALS were included from across 19 French FILSLAN network centers. Baseline was defined as the treatment initiation date. Main endpoints were the ALSFRS-R progression rate and plasmatic neurofilament light chain (NfL) levels at baseline and 12 months after baseline. Results In the Tofersen Cohort (N=46), within-group comparisons showed that the mean ALS functional rating scale revised (ALSFRS-R) progression rate slowed from 0.53 ± 0.5 at baseline to 0.22 ± 0.3 point/month at 12 months ( P =.006). NfL levels significantly decreased from 89.0 ± 9.0 pg/ml at baseline to 29.2 ± 19.5.5 at 12 months ( P =.004). Exploratory comparisons with a propensity score (PS) matched historical cohort (39 matched pairs) using a mixed-effects model, ALSFRS-R progression rate at baseline, 6 months, and 12 months after baseline, showed no statistically significant differences between groups P =.30, whereas longitudinal ALSFRS-R scores differed significantly between groups (time-treatment interaction P =.006). The mean survival of the PS matched population was longer in the Tofersen Cohort (42.6 months) than the Historical Cohort (31.8 months) P =.004. Time-dependent adjusted cox analysis showed that Tofersen was associated with a reduction in mortality risk (adjusted HR=0.34; 95% CI, 0.12-0.91; P =.03). Conclusion Tofersen seems to be associated with slower functional decline and reduced NfL levels. While limitations of retrospective design and ALSFRS-R sensitivity must be acknowledged, these findings provide real-world evidence suggesting a clinical benefit of Tofersen.

Mayo Clinic Proceedings Innovations Quality & OutcomesVol. 10(5)
Université Claude Bernard Lyon 1 (FR), Université de Tours (FR), Délégation Paris 5 (FR), Centre National de la Recherche Scientifique (FR), Université de Bordeaux (FR), Inserm (FR), Université de Bourgogne (FR), Université Paris Cité (FR), Alliance for Clinical Trials in Oncology (US), Sorbonne Université (FR), Assistance Publique Hôpitaux de Marseille (FR), Sorbonne Paris Cité (FR), Centre Hospitalier Universitaire de Montpellier (FR), Imaging, Brain, and Neuropsychiatry (FR), Centre Hospitalier Universitaire de Tours (FR), Assistance Publique – Hôpitaux de Paris (FR), Hospices Civils de Lyon (FR), University of Clermont Auvergne (FR), Laboratoire National de Référence (MA), Pitié-Salpêtrière Hospital (FR), Institut NeuroMyoGène (FR), Neurocentre Magendie (FR), Mother Hospital (IN), Observatoire de la Côte d’Azur (FR), Centre Hospitalier Universitaire de Clermont-Ferrand (FR), Institute for Neurosciences of Montpellier (FR), Maison des Sciences sociales et des Humanités de Dijon (FR), Clermont Université (FR), Centre Hospitalier Universitaire de Saint-Étienne (FR), Institut de Recherche pour le Développement (FR), French Clinical Research Infrastructure Network (FR), Université d'Angers (FR), Université de Limoges (FR)
Biogen, Institut National de la Santé et de la Recherche Médicale, Centre National de la Recherche Scientifique, Université de Bordeaux, Hospices Civils de Lyon, Université François-Rabelais, Université de Montpellier, Universite Angers, Sorbonne Université, Université de Limoges
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Amyotrophic Lateral Sclerosis Research
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