On April 25 2023, the U.S. Food and Drug Administration (FDA) granted accelerated approval to tofersen (trade name Qalsody) for the treatment of Superoxide Dismutase 1 (SOD1) associated amyotrophic lateral sclerosis (ALS) . The clinical trial failed to meet its primary endpoint; however, approval was granted based on a biomarker response: reduced plasma levels of neurofilament light protein . Although confirmatory studies to assess the impact on disease progression must still be performed, results from the open-label study suggest that tofersen may slow down disease progression.
Tofersen is the first intrathecally delivered RNase H antisense oligonucleotide (ASO) to receive FDA approval and the second approved intrathecal ASO. Nusinersen, an intrathecally delivered splice modulating ASO for the treatment of spinal muscular atrophy, received FDA approval in 2016 . Tofersen is the fifth ASO to be approved based on biomarker results, joining eteplirsen, golodirsen, viltolarsen, and casimersen, all approved for the treatment of Duchenne muscular dystrophy in patients with eligible mutations . With the approval of tofersen, the total number of ASO therapies approved by FDA and/or the European Medicines Agency comes to 15 (Table 1).