The study followed people with SOD1-ALS, a hereditary form of amyotrophic lateral sclerosis caused by variants in the SOD1 gene. This form represents roughly 2% of ALS cases and typically carries a life expectancy of two to three years from symptom onset. Tofersen (also called Qalsody) is an antisense oligonucleotide that reduces production of the mutated SOD1 protein. The drug was developed by researchers working with Biogen and Ionis Pharmaceuticals and received FDA approval in 2023 through an accelerated pathway.
A phase 3 trial ran for six months and then 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. Researchers report that long-term tofersen use delayed symptom progression and death. About one-quarter of participants experienced stabilization or functional improvement over roughly three years, with gains in grip strength and respiratory function. Overall progression was much slower than expected for typical SOD1-ALS, and at least half of participants were alive nearly five years after the study began, versus the usual survival a little more than two years after symptoms start.
The comparison between people who started tofersen immediately and those who began after six months did not reach statistical significance at three years; the authors note this may reflect the trial design, which allowed placebo participants to switch to active treatment after six months. Common adverse events were headache, procedural pain, falls, back pain and extremity pain. Nine participants (9%) had more serious, mainly inflammatory, neurological events that were treated successfully. Patient reports described meaningful benefits, and a multisite trial is now testing tofersen in people with known SOD1 variants but no symptoms. Biogen funded the study and provided the drug; several authors disclosed consulting and advisory relationships, while Washington University reports no financial interest in tofersen.
Difficult words
- hereditary — Passed down from parent to child.
- variant — A different form of a gene.variants
- antisense oligonucleotide — Short strand of genetic material that blocks RNA.
- accelerated pathway — Faster regulatory process for drug approval.
- open-label extension — Study phase where all participants receive treatment.
- stabilization — A state of little or no change.
- statistical significance — A result unlikely to occur by chance.
- adverse event — An unwanted medical problem during a trial.adverse events
- placebo — An inactive substance given as control.
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Discussion questions
- What possible benefits and risks do you see in testing tofersen in people who have SOD1 variants but no symptoms?
- How does allowing placebo participants to switch to active treatment affect how we interpret the trial results?
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