Tofersen Fails to Slow Progression in SOD1 ALS

In patients with amyotrophic lateral sclerosis (ALS) and SOD1 mutations, accumulation of misfolded aggregates of superoxide dismutase 1 (SOD1) protein is thought to result in neurotoxicity. Tofersen is an investigational (not FDA-approved) antisense oligonucleotide–targeting SOD1 synthesis. In this industry-sponsored phase 3 trial, adults with SOD1 ALS were randomized to intrathecal injections of tofersen 100 mg (72 patients) or placebo (36 patients).

Eight injections were given over 24 weeks: once every 2 weeks for 3 doses, then every 4 weeks for 5 doses. The primary endpoint, assessed in 60 patients with faster-progressing disease, was change on the Revised Amyotrophic Lateral Sclerosis Functional Rating Scale (ALSFRS-R) from baseline to w…