Tofersen improves functional independence in SOD-1 ALS

Key takeaways:

• Neurofilament light chain and cerebrospinal fluid phosphorylated neurofilament heavy chain biomarkers were significantly reduced.
• Most treatment-related adverse events were mild to moderate in severity.

Treatment with tofersen in patients with superoxide 1 dismutase 1 ALS was linked to preservation of motor function, maintenance of muscle strength and reduction of disease-specific biomarkers, data show.

“Mutations in SOD1, the gene encoding superoxide 1 dismutase-1 (SOD1), are present in 1% to 2% of all amyotrophic lateral sclerosis patients,” Sean E. Smith, MD, MPHS, assistant professor in the department of neurology at Washington University of St. Louis School of Medicine, and colleagues wrote in the Annals of Clinical and Translational Neurology. “Tofersen is an antisense oligonucleotide that binds to and facilitates RNase-mediated degradation of SOD1 messenger RNA, thereby reducing SOD1 protein production.”

Prior research has established that treatment with tofersen (Qalsody, Biogen) led to slowing of disease progression in ALS, as well as disease stabilization with recovery of function in some patients, the researchers wrote.

They aimed to report clinical outcomes due to tofersen administration in patients with SOD1 ALS, along with subsequent effects of the drug on outcome measures.

Their retrospective, single-center observational study included seven adults (median age 64 years; average disease duration, 62.7 months) with confirmed SOD1 ALS diagnoses who received 100 mg intrathecal tofersen of three loading doses at 14-day intervals preceded by monthly maintenance dosing.

Cerebrospinal fluid phosphorylated neurofilament heavy chain (CSF pNFH) as well as serum neurofilament light chain (NfL) biomarkers were taken via standard assays, while multiple standard clinical assessments including the Revised ALS Functonal Rating Scale (ALSFRS-R), ALS Assessment Questionnaire 5-Item, 10-meter walk test measured physical and quality-of-life metrics.

Results showed all seven patients demonstrated significant and sustained reduction of serum NfL (57.9%) and CSF pNFH (67.6%) with tofersen.

Smith and colleagues also reported disease stabilization associated with tofersen by a mean change of 1.1 in ALSFRS-R total score, along with demonstrable improvement in functional independence from a mean change of 5.13 points on the functional independence measure motor score.

Further data analysis showed that tofersen administration led to muscle strength improvement in five patients as measured by handheld dynamometry.

The majority of reported adverse treatment-related events were mild to moderate in severity, including muscle pain and other myalgias consistent with reportage in previous studies.

“For decades, neurologists and scientists have thought that disease-modifying therapies for ALS would either slow down or stop further progression of the disease,” Kuldip Dave, PhD, senior vice president of research at the ALS Association, said in a release issued by the organization. “The fact that these data were collected during standard of care treatment in real-world settings further validate that functional recovery is real and significant.”

Reference:

Study demonstrates sustained stabilization and functional recovery in SOD1-ALS patients treated with Qalsody (Tofersen). https://www.als.org/stories-news/study-demonstrates-sustained-stabilization-and-functional-recovery-sod1-als-patients. Published Jan. 15, 2025. Accessed Jan. 16, 2025.