International Alliance

Supports a claim in this answer

the early trial did not meet its main endpoint at 28 weeks but showed promising biomarker changes and longer-term functional trends

✓Supports this

“The most common reported side effects of tofersen include pain in the arm, back, legs, muscle or joints.”

Lists this first among the most common side effects. The same list also records raised proteins or blood cells in the cerebrospinal fluid, and fever.

Pain in the arm, back, legs, muscle or joints

Reported Side Effects

✓Supports this

“Tofersen is given every two weeks for the first three doses and then as a maintenance dose once every four weeks.”

Gives the schedule. The four weekly dose is a maintenance dose, so the lumbar punctures continue for as long as someone stays on treatment rather than stopping after a course.

The treated individual will receive a dose every two weeks for three times and then a maintenance dose once every four weeks.

Dose and Administration

✓Supports this

“Tofersen can only be given in a healthcare facility equipped for intrathecal administration, because delivery needs highly specialised personnel and close monitoring.”

States the setting requirement and the reason for it. This is why tofersen is not something that can be arranged locally like a tablet or a routine infusion.

Because its delivery requires highly specialized personnel and close monitoring, it can only be delivered in a healthcare facility equipped for intrathecal administration.

Dose and Administration

✓Supports this

“More serious reported side effects of tofersen include myelitis or radiculitis, papilledema with raised intracranial pressure, and aseptic meningitis.”

Lists three more serious side effects under this heading: inflammation of the spinal cord or irritation of the nerve roots, swelling of the optic nerve with raised pressure inside the skull, and inflammation of the brain linings. The quote is the first of the three; the answer carries all three because the page presents them as one set.

Inflammation of the spinal cord (myelitis) and/or irritation of the nerve roots (radiculitis)

Reported Side Effects

✓Supports this

“Beyond its primary endpoint, tofersen lowered a marker of nerve damage and the longer follow-up favoured people who started treatment sooner.”

Describes both parts. Lowering SOD1 produced a significant fall in neurofilament light chain, a marker of nerve damage, and secondary measures of movement, breathing, strength and quality of life pointed the right way. At twelve months the group treated from the start was doing better than the group that started six months later.

Based on the available evidence, it is the opinion of the SAC that tofersen is likely to have a significant benefit for people living with ALS/MND caused by a mutation in the SOD1 gene, particularly in those starting treatment earlier.

Summary

Further reading

Overview of trial results and who tofersen is for