Tofersen

Tofersen is under an intrathecally administered antisense oligonucleotide targeting the mutated SOD1 gene that causes amyotrophic lateral sclerosis (ALS). Although there were various causes of ALS, 2% of ALS cases are due to SOD1 mutations, with more than 200 SOD1 mutations documented. Tofersen was granted accelerated approval from the FDA on April 25, 2023, as the first treatment for adults with ALS caused by SOD1 mutation. Continual FDA approval is contingent on clinical benefits from ongoing trials, particularly the Phase 3 ATLAST study in people with presymptomatic SOD1-ALS.

Tofersen demonstrated efficacy in reducing the concentration of SOD1 in CSF and of neurofilament light chains in plasma over 28 weeks, although the ALS Functional Rating Scale–Revised did not improve. However, it could potentially be due to the short timeframe of tofersen treatment, and more longterm trials are being conducted to confirm this hypothesis.

Tofersen is indicated for the treatment of amyotrophic lateral sclerosis (ALS) in adults who have a mutation in the superoxide dismutase 1 (SOD1) gene. This indication is approved under accelerated approval based on the reduction in plasma neurofilament light chain (NfL) observed in patients treated with tofersen. Continued approval for this indication may be contingent upon verification of clinical benefit in confirmatory trials.