Tofersen: clinical use

Prescribing considerations

• Confirm adult ALS associated with an SOD1 mutation before initiation.
• Initiation should be by a physician experienced in ALS management; administration requires lumbar-puncture expertise.
• Assess factors affecting safe intrathecal access; consider imaging guidance or sedation when clinically indicated.
• Experience in older adults is limited. Use has not been studied in renal or hepatic impairment or established in people under 18.
• Review clinical response and the appropriateness of continuing therapy regularly.

Contraindications and cautions

• Hypersensitivity to tofersen or any excipient.
• Use caution where lumbar puncture cannot be performed safely.

Monitoring

• Assess for lumbar-puncture complications, including headache, back pain and infection.
• Promptly investigate symptoms compatible with myelitis, radiculitis, papilloedema, increased intracranial pressure or aseptic meningitis.
• Consider platelet count and coagulation testing when clinically indicated.
• Consider first-morning urine protein testing when clinically indicated and investigate persistent elevation.
• Monitor clinical presentation and response because benefit varies.

Clinical pharmacology

Tofersen is an antisense oligonucleotide complementary to the untranslated region of SOD1 messenger RNA. Hybridisation triggers RNase-H-mediated degradation, reducing SOD1 synthesis. It is degraded by exonucleases and neither induces nor inhibits CYP450 enzymes.

Formulation and product differences

• The UK product is a preservative-free, single-use intrathecal solution supplied in a vial.
• Do not dilute or mix with other medicines.
• Use only clear, colourless to slightly yellow solution without visible particles; do not shake.
• Store refrigerated, protect from light and do not freeze.

Injection

Route: Parenteral

Strengths: 100 mg