<p>Tofersen (QALSODY^®) is the first drug approved for the treatment of amyotrophic lateral sclerosis (ALS) associated with superoxide dismutase&#xa0;1 (<i>SOD1</i>) mutations. Tofersen is an antisense oligonucleotide that induces <i>SOD1</i> mRNA degradation. In the 28-week, placebo-controlled, multinational, phase&#xa0;III VALOR trial, intrathecally administered tofersen reduced plasma concentrations of neurofilament proteins (biomarker for neuro-axonal injury) and total SOD1 protein in cerebrospinal fluid in patients with <i>SOD1</i> mutation-associated ALS. These reductions were sustained in a long-term, open-label extension study. The decline in functional outcomes was not significantly reduced with tofersen treatment compared with placebo in the 28-week phase III trial, although in the longer-term open-label study, early tofersen initiation was associated with slowed functional decline versus delayed tofersen initiation. Tofersen had an acceptable tolerability profile in clinical trials with a favourable benefit-to-risk balance. In summary, tofersen is a new disease-modifying therapy for patients with ALS attributed to an <i>SOD1</i> mutation, offering reductions in levels of a biomarker associated with neurodegeneration and disease progression, with an acceptable tolerability profile.</p>