Clinical and patient‐reported outcomes and neurofilament response during tofersen treatment in SOD1‐related ALS—A multicenter observational study over 18months

Introduction/AimsIn amyotrophic lateral sclerosis (ALS) caused by SOD1 mutations (SOD1‐ALS), tofersen received accelerated approval in the United States and is available via expanded access programs (EAP) outside the United States. This multicenter study investigates clinical and patient‐reported outcomes (PRO) and serum neurofilament light chain (sNfL) during tofersen treatment in an EAP in Germany.MethodsSixteen SOD1‐ALS patients receiving tofersen for at least 6 months were analyzed. The ALS progression rate (ALS‐PR), as measured by the monthly change of the ALS functional rating scale—revised (ALSFRS‐R), slow vital capacity (SVC), and sNfL were investigated. PRO included the Measure Yourself Medical Outcome Profile (MYMOP2), Treatment Satisfaction Questionnaire for Medication (TSQM‐9), and Net Promoter Score (NPS).ResultsMean tofersen treatment was 11 months (6–18 months). ALS‐PR showed a mean change of −0.2 (range 0 to −1.1) and relative reduction by 25%. Seven patients demonstrated increased ALSFRS‐R. SVC was stable (mean 88%, range −15% to +28%). sNfL decreased in all patients except one heterozygous D91A‐SOD1 mutation carrier (mean change of sNfL −58%, range −91 to +27%, p