Tofersen: A Novel Option for the Treatment of Amyotrophic Lateral Sclerosis.

OBJECTIVE This review summarizes current evidence on the efficacy and safety of tofersen (Qalsody) in treating amyotrophic lateral sclerosis (ALS).

DATA SOURCES PubMed, MEDLINE, Google Scholar, and ClinicalTrials.gov were searched using the keywords: Qalsody, BIIB067, antisense oligonucleotides, SOD1, and amyotrophic lateral sclerosis. Articles published from inception to November 2025 were included.

STUDY SELECTION AND DATA EXTRACTION English-language studies assessing the pharmacokinetics, pharmacology, efficacy, and safety of tofersen were included. Prescribing information and real-world evidence were also reviewed.

DATA SYNTHESIS Tofersen is an intrathecally administered antisense oligonucleotide targeting superoxide dismutase 1 (SOD1) mRNA. Early trials demonstrate dose-dependent reductions in cerebrospinal fluid (CSF) SOD1 protein levels of -33% and slower ALS Functional Rating Scale (ALSFRS-R) decline compared to placebo (-1.19 vs -5.63 points). In Phase 3 trials, tofersen reduced CSF SOD1 by 29% and plasma neurofilament light chain (NfL) by 60%, while biomarkers increased in the placebo group. There was no significant difference in ALSFRS-R decline between tofersen and placebo (-6.98 vs -8.14; P = 0.97). Real-world data show favorable patient-related outcomes and improvement in ALSFRS-R. Adverse effects are primarily lumbar puncture related with serious neurologic events documented in 7% of tofersen recipients.Relevance to Patient Care and Clinical Practice in Comparison to Existing Drugs:As the first Food and Drug Administration (FDA)-approved gene-directed therapy for SOD1 ALS, tofersen directly targets the underlying genetic cause. Barriers include the need for genetic confirmation and intrathecal administration.

CONCLUSION Tofersen provides a promising targeted treatment option for pathogenic SOD1 ALS. Ongoing studies will clarify its long-term clinical impact.