A long-term study evaluated tofersen for SOD1-ALS, a rare genetic form of amyotrophic lateral sclerosis that accounts for roughly 2% of ALS cases. Average life expectancy for people with SOD1-ALS is two to three years from symptom onset. Tofersen is an antisense oligonucleotide that lowers production of the mutated SOD1 protein. The drug received FDA approval in 2023 under an accelerated pathway.
The phase 3 trial lasted six months and continued as an open-label extension co-led by Washington University School of Medicine in St. Louis. Of 108 original participants, 46 completed follow-up after 3.5 to 5.5 years. Long-term use delayed symptom progression and death, and about one-quarter of participants showed stabilization or improvement over roughly three years, including better grip strength and respiratory function.
Common side effects included headache, procedural pain, falls and back or limb pain. Nine participants (9%) had more serious inflammatory neurological side effects, which were treated successfully. A multisite trial now tests whether tofersen can prevent or delay disease in people with the gene variant but no symptoms. Biogen funded the study and provided the drug, and investigators disclosed ties to the company.
Difficult words
- antisense oligonucleotide — a short lab-made molecule that blocks a gene
- mutate — to change in genetic material or formmutated
- open-label extension — a study phase where participants know the treatment
- stabilization — a state of little or no further change
- inflammatory — relating to swelling or immune-system reaction
- follow-up — a later check to see health or progress
Tip: hover, focus or tap highlighted words in the article to see quick definitions while you read or listen.
Discussion questions
- Would you take a drug that can slow a serious disease but has some risk of inflammatory side effects? Why or why not?
- The study continued as an open-label extension with long follow-up. How important is long-term follow-up for you when judging a new treatment, and why?
- The article says a new trial will test use in people with the gene variant but no symptoms. What are the advantages and concerns of treating people before symptoms start?
Related articles
New ultrasound method improves diagnosis of breast masses
Researchers developed a new ultrasound signal-processing method that distinguishes fluid cysts from solid breast masses. In initial patient tests doctors identified masses correctly far more often than with conventional ultrasound, which could reduce biopsies and follow-ups.
