Tofersen for Treatment of Familial Amyotrophic Lateral Sclerosis

An early-stage trial for tofersen (BIIB067; Biogen, Cambridge, MA) an investigational drug for amyotrophic lateral sclerosis (ALS), showed that the drug is linked to slower progression of a form of the disease caused by mutations in the superoxide dismutase 1 (SOD1) gene. Results of the study will be presented at the American Academy of Neurology Annual Meeting in May. 

About 10% of ALS cases are genetic and about 20% of those cases are caused by SOD1 gene mutations. The study involved 50 people with ALS who had an SOD1 genetic mutation. Patients received 5 doses of 20mg, 40mg, 60mg, or 100mg of the drug over 3 months. 

The study revealed that 10 people who received 100mg of the drug had a 37% reduction of the SOD1 protein in spinal fluid compared to 12 people who received a placebo. Those on the 100mg dose scored better on tests that measure breathing capacity, muscle strength, and functioning on activities than patients on a placebo. 

On a scale that measures functioning on activities, patients who received the 100mg dose had an average decline of 1.1 points compared to those on a placebo, who averaged a decline of 5.3 points.

Considering the short duration of treatment, the difference between patients who received 100mg of the drug and those who received placebo was more apparent in those with rapidly progressing SOD1 ALS. 

“The treatment that we researched in this study, an antisense oligonucleotide called tofersen (BIIB067), works by targeting and reducing protein created by the mutated gene,” said Timothy M. Miller, MD, PhD, of the Washington University School of Medicine. “That mutated protein is toxic and leads to ALS by damaging the nerve cells that control movement. Our research aimed to decrease the production of that protein. Lower concentrations of the protein in the spinal fluid suggest that there were also lower concentrations in the brain and spinal cord. Such reductions could lead to preservation of motor neurons and slow progression of the disease, but more study is needed to examine this further.”