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Serious Neurologic Adverse Events in Tofersen Clinical Trials for Amyotrophic Lateral Sclerosis
Alexandra Lovett1, Sowmya Chary1, Suma Babu2
1Biogen, Cambridge, Massachusetts, USA.
Muscle & Nerve
|February 28, 2025
Summary
Serious neurologic adverse events (AEs) occurred in tofersen trials for superoxide dismutase 1 mutations amyotrophic lateral sclerosis (SOD1-ALS). Most events resolved, but some led to treatment discontinuation, informing the drug's benefit/risk profile.
Area of Science:
- Neurology
- Pharmacology
- Genetics
Background:
- Tofersen is approved for treating amyotrophic lateral sclerosis (ALS) associated with superoxide dismutase 1 mutations (SOD1-ALS).
- Antisense oligonucleotides (ASOs) can exhibit pro-inflammatory properties, necessitating safety monitoring.
Purpose of the Study:
- To report and characterize serious neurologic adverse events (AEs) observed during tofersen clinical trials for SOD1-ALS.
- To inform the ongoing assessment of tofersen's benefit/risk profile in SOD1-ALS patients.
Main Methods:
- Systematic description of serious neurologic AEs, including myelitis, radiculitis, aseptic meningitis, and papilledema.
- AEs were defined per International Conference for Harmonization guidelines and diagnosed by investigators based on clinical presentation and workup.
Main Results:
- Ten participants (approx. 7%) experienced 12 serious neurologic AEs: 4 myelitis, 2 radiculitis, 2 aseptic meningitis, 4 intracranial hypertension/papilledema.
- Most events resolved spontaneously or with treatment modification; three led to discontinuation, but most participants continued tofersen.
- No serious neurologic AEs were life-threatening or fatal.
Conclusions:
- Neurologic AEs such as myelitis, radiculitis, and papilledema, not previously reported with ASO treatment, occurred with tofersen.
- These findings are crucial for evaluating the overall benefit/risk of tofersen for SOD1-ALS.
- Continued safety data collection will further refine tofersen's safety profile in SOD1-ALS.
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