On April 25^th, 2023, the U.S. Food and Drug Administration (FDA) approved Qalsody^TM (tofersen) for the treatment of amyotrophic lateral sclerosis (ALS) associated with a mutation in the superoxide dismutase 1 (SOD1) gene (SOD1-ALS).[1] The accelerated approval for Qalsody^TM was based on a reduction in levels of plasma neurofilament light (NfL), a biomarker associated with neuronal injury and neurodegeneration.[2] Qalsody^TM was developed in a partnership between Ionis Pharmaceuticals, Inc. and Biogen Inc.[3]

ALS is a neurodegenerative disorder that causes muscle atrophy resulting in loss of movement and ultimately fatal respiratory failure.[4] Mutations in the SOD1 gene are the most frequent among more than forty genes associated with ALS.[5] Although approximately 10% of affected persons show a familial predisposition, most cases are classified as sporadic.[6]

Qalsody^TM is an antisense oligonucleotide therapy that targets expression of the superoxide dismutase 1 gene.[7] Qalsody^TM was tested in a randomized clinical trial involving 147 patients with weakness attributable to ALS and a confirmed SOD-1 mutation.[8] Patients receiving Qalsody^TM demonstrated nominally significant reductions in plasma NfL levels after 28 weeks compared with placebo.[9]

Qalsody^TM 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.[10] 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.”[11]