On April 25th, 2023, the U.S. Food and Drug Administration (FDA) approved QalsodyTM (tofersen) for the treatment of amyotrophic lateral sclerosis (ALS) associated with a mutation in the superoxide dismutase 1 (SOD1) gene (SOD1-ALS). The accelerated approval for QalsodyTM was based on a reduction in levels of plasma neurofilament light (NfL), a biomarker associated with neuronal injury and neurodegeneration. QalsodyTM was developed in a partnership between Ionis Pharmaceuticals, Inc. and Biogen Inc.
ALS is a neurodegenerative disorder that causes muscle atrophy resulting in loss of movement and ultimately fatal respiratory failure. Mutations in the SOD1 gene are the most frequent among more than forty genes associated with ALS. Although approximately 10% of affected persons show a familial predisposition, most cases are classified as sporadic.
QalsodyTM is an antisense oligonucleotide therapy that targets expression of the superoxide dismutase 1 gene. QalsodyTM was tested in a randomized clinical trial involving 147 patients with weakness attributable to ALS and a confirmed SOD-1 mutation. Patients receiving QalsodyTM demonstrated nominally significant reductions in plasma NfL levels after 28 weeks compared with placebo.
QalsodyTM is approved under the accelerated approval pathway, which requires that drugs address an unmet medical need and demonstrate an effect on a surrogate endpoint with a predictable clinical benefit. Christopher A. Viehbacher, President and CEO of Biogen noted that the approval indicates “for the first time, consensus that neurofilament can be used as a surrogate marker reasonably likely to predict clinical benefit in SOD1-ALS. We believe this important scientific advancement will further accelerate innovative drug development for ALS.”