Section 08 · Monograph
Tofersen
Reviewed Nov 2026FDA label
QalsodyAntisense oligonucleotide
- Forms
- Intrathecal: 100mg/15mL
- Dose
- 3 loading doses q14 days, then maintenance q28 days
- MOA
- Reduces SOD1 mRNA/protein
Indications
- Treatment of amyotrophic lateral sclerosis (ALS) in adults who have a mutation in the superoxide dismutase 1 (SOD1) gene (SOD1-ALS)FDA-labeled
Off-Label Uses
- Investigational use in presymptomatic SOD1 mutation carriers to delay onset of clinical ALS (studied in the ATLAS trial)Off-label
Mechanism of Action
- Antisense oligonucleotide (ASO) designed to bind SOD1 mRNA
- Reduces synthesis of SOD1 protein through RNase H1-mediated degradation of SOD1 mRNA
- Reduction in SOD1 protein, including mutant/toxic forms, is thought to slow motor neuron degeneration
- Approved under accelerated approval based on reduction in plasma neurofilament light chain (NfL), a biomarker of axonal injury
Full Dosing
Adult / usual
- Loading dose: 100 mg (15 mL) intrathecally every 14 days for the first 3 doses
- Maintenance dose: 100 mg intrathecally every 28 days thereafter
- Administered via intrathecal (lumbar puncture) injection by a healthcare provider only
Renal
- No dose adjustment established for renal or hepatic impairment
Contraindications
- No absolute contraindications identified; use with caution given risk of serious neurologic adverse reactions including myelitis, radiculitis, and elevated intracranial pressure with papilledema
Drug Interactions
- No formal drug-drug interaction studies conducted; low systemic exposure after intrathecal administration limits likelihood of systemic interactions
- Caution with concurrent anticoagulant or antiplatelet therapy given intrathecal administration/lumbar puncture bleeding risk
Adverse Effects
- Serious: myelitis (spinal cord inflammation)
- Serious: radiculitis
- Serious: elevated intracranial pressure with papilledema
- Serious: aseptic meningitis
- Common: pain (procedural/back/extremity pain)
- Common: fatigue
- Common: arthralgia
- Common: CSF pleocytosis and elevated CSF protein
- Common: headache post-lumbar-puncture
Monitoring Parameters
- Baseline and periodic neurologic exams for signs of myelitis/radiculitis
- CSF cell count, protein, and glucose before and periodically during treatment
- Signs/symptoms of increased intracranial pressure (headache, nausea, vomiting, visual changes) and fundoscopic exam for papilledema if suspected
- Plasma neurofilament light chain (NfL) trends where clinically used
- SOD1 genetic confirmation prior to initiation
Pregnancy & Lactation
- No adequate human data on use in pregnancy; animal reproduction studies not fully characterized in labeling — use only if potential benefit justifies potential fetal risk
- No data on presence in human milk or effects on breastfed infant; consider developmental and health benefits of breastfeeding along with mother's clinical need