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Tofersen

  • RNA medicine
  • Not established
  • Identity checked
  • Sources last checked 2026-09-04

This page shows what was measured, who it was measured in, and what that does not settle.

What Tofersen does in the body

Used for a rare inherited form of the muscle-wasting disease ALS.

In this form of ALS a faulty version of one protein poisons motor neurons. Tofersen is a short strand injected into the spinal fluid that pairs with the instructions for that protein so an enzyme destroys them, and the cell makes less of the poison. In the pivotal trial the amount of a marker of nerve damage in the blood fell sharply. The measure of how patients actually functioned did not separate from placebo.

What happened in people

A blood sign of nerve damage fell by more than half, but physical abilities did not clearly improve.

Reviewed first-read answer

Where this came from

A person wrote this and a reviewer approved it against this exact record. It carries no effect size.

A reviewer approved this against this record. The reviewed-claim record carrying the exact population and effect size does not exist yet.

No source is stored against this line.

The limit that matters most

A better blood result does not show that people will keep walking, swallowing or breathing longer.

Where it acts
Spinal cord and motor cortex neurons, reached through cerebrospinal fluid
Kind of result
A number that stands in for health
Supervision
Professional supervision is normally required. It is a prescription or clinician-administered medicine where it is approved.

What the registries record it as

  • The substance registry classes this as nucleicacid.

    FDA substance registry · 2NU6F9601K · read 2026-08-29

  • Its recorded molecular formula is C230H317N72O123P19S15, weighing 7127.86.

    US prescribing information · 81356b45-1cb7-4eef-88ea-e44cc18b47c5 · read 2026-08-30

Where each sentence above came from

No recorded sentence describes the change this makes in a way that stands on its own. The page opens with what it is taken for instead, and the recorded explanation follows below.

Shown as the opening line on this page.

The limit a reviewer approved as the one that matters most here.

The four opening statements run to 105 words.

Words this page uses

Four words worth knowing first

Chosen from what this page shows, with each one explained before the word it depends on.

Protein

A protein is a folded chain your body builds to do a specific job.

A picture of it, and where the picture fails

A protein is like a tool bent into one shape for one task.

Where that stops being true. A tool keeps its shape. A protein can change shape and stop working.

What people get wrong. Protein in food and a protein in the body are related but not the same thing.

A polymer of amino acids folded into a defined structure that determines its function.

Gene

A gene is a stretch of instructions for building one protein.

A picture of it, and where the picture fails

A gene is like one page of a building plan.

Where that stops being true. A page is read the same way every time. A gene can be read more or less often.

What people get wrong. Having a gene is often read as having a trait. Whether it is used matters as much.

A segment of DNA that encodes a functional product, usually a protein.

Messenger RNA

Messenger RNA is a working copy of one gene, carried to where proteins are built.

A picture of it, and where the picture fails

It is like a photocopy of one plan page, taken to the workshop.

Where that stops being true. A photocopy lasts. This copy is destroyed soon after use, on purpose.

What people get wrong. It is often thought to change the gene. It is a copy, and it does not alter the original.

A single-stranded transcript of a gene that ribosomes translate into a protein.

Small interfering RNA

A small interfering RNA is a short piece that makes a cell destroy one working copy.

A picture of it, and where the picture fails

It is like a note telling the workshop to shred one plan page.

Where that stops being true. A note is read once. This keeps working for months after one injection.

What people get wrong. It is often described as gene editing. It leaves the gene untouched.

A short double-stranded RNA that directs the RNA-induced silencing complex to cleave a complementary transcript.

What happened in peopleRead from sources, not yet reviewed

What happened in people

Each card is one study: the exact question it asked, who was in it, and whether it showed what it set out to show.

Change from baseline to week 28 in ALSFRS-R total score in participants predicted to progress faster

The study did not show it

Who was studied
VALOR Part C (NCT02623699)
How many people
108
Study design
Phase 3
Compared against
Not recorded for this study
Kind of result
A number that stands in for health
What was found
p=0.97 (difference 1.2 points, 95 percent CI -3.2 to 5.5)
Repeated elsewhere
Unreplicated

What this does not prove. A study that did not show an effect does not show that no effect exists anywhere.

The limits of this study, and where it came from

Main limit. Neurologic serious adverse events in 7 percent of tofersen recipients, including myelitis and radiculitis; lumbar-puncture-related events common in both arms

How far it carries. This study is recorded from the curated record, not from the registry match.

Form and route. Intrathecal injection of a mixed-backbone 2-prime-MOE gapmer

Interval reported. Not recorded in this summary

Written into the record, not signed off as a reviewed claim.

What we know
RNAWiki holds 1 written-up human studies for this substance, each with the question it asked.
How we know it
Each card names the study, the number of people and what the study set out to measure.
What this does not prove
These summaries were written by a person and have not been signed off as reviewed claims.
Why it matters
A study that failed is as informative as one that worked, and both are here.
What we still do not know
No reviewed claim exists, so no exact population, effect size or interval is published yet.

What it changes in the bodyRead from sources, not yet reviewed

The path through the body

From what a person takes to what changes. A solid line is a step measured in people. A dashed line is a step nobody has measured that way.

  1. Start

    Tofersen

    What a person takes: Intrathecal injection of a mixed-backbone 2-prime-MOE gapmer.

    The measurement behind this step

    Preservative-free solution given by lumbar puncture, three loading doses at 14-day intervals and then monthly. No carrier and no ligand; the phosphorothioate content alone drives cellular uptake.

  2. Getting in

    Intrathecal injection by lumbar puncture

    The drug is injected into the fluid around the spinal cord, because nothing given into a vein reaches motor neurons.

    Described, with no measurement named. No measurement is named for this step, so it is drawn as an unconfirmed link.

    The measurement behind this step

    Bolus intrathecal administration after three loading doses, then monthly. Distribution follows cerebrospinal fluid bulk flow to spinal cord and brain, with a long tissue residence time.

  3. Reaching the cell

    Free uptake into motor neurons and glia

    Nerve cells take the strand in directly, with no packaging around it.

    Described, with no measurement named. No measurement is named for this step, so it is drawn as an unconfirmed link.

    The measurement behind this step

    Gymnotic uptake driven by phosphorothioate protein binding, followed by endosomal escape into nucleus and cytoplasm. Uptake is not neuron-selective; glia take up drug as well.

  4. What it acts on

    Hybridising to SOD1 messenger RNA

    It pairs with the instructions for the faulty protein.

    Described, with no measurement named. No measurement is named for this step, so it is drawn as an unconfirmed link.

    The measurement behind this step

    The 10-base deoxynucleotide gap forms a heteroduplex with SOD1 mRNA; the flanking MOE wings raise affinity and block nuclease degradation. The drug does not discriminate mutant from wild-type transcript.

  5. The change it makes

    RNase H1 destroys the transcript

    An enzyme already present in the cell recognises the pairing and cuts the messenger strand.

    Described, with no measurement named. No measurement is named for this step, so it is drawn as an unconfirmed link.

    The measurement behind this step

    RNase H1 cleaves the RNA strand of the DNA:RNA heteroduplex. The catalytic mechanism means one oligonucleotide molecule degrades many transcripts, sustaining knockdown between monthly doses.

  6. What that does for a person

    SOD1 protein falls and neurofilament release falls with it

    Less of the toxic protein is made, and the blood marker of nerve breakdown drops sharply. Whether that changes what the patient can do is unproven.

    Measured in people. Written by a person from the study named beside the step. Not signed off as a reviewed claim.

    The measurement behind this step

    Cerebrospinal fluid SOD1 decreases and plasma neurofilament light chain falls by 55 percent at week 28. The functional scale in the same trial showed no separation from placebo, which is the central unresolved fact about this drug.

No suggested links are held for this record, so nothing is hidden from this path.

What we know
The record describes 5 steps from taking it to an effect in a person.
How we know it
Each step names the study behind it in the technical detail beside it.
What this does not prove
A change inside the body is a reason to look. It is not a result in a person.
Why it matters
A reader can see exactly where the chain stops being measured in people.
What we still do not know
No reviewed claim binds any of these steps to a named population.

What is missing or unclearRead from sources, not yet reviewed

Were people like you studied?

RNAWiki cannot tell whether a study fits you. It can show who was in it, and where the result stops carrying.

Who was studied

People similar to this profile were included.

  • Adults with genetically confirmed SOD1-ALS, by intrathecal injection, after loading doses and then monthly.

Who is missing from the studies

  • Which groups were under-represented in the studies has not been recorded for this substance. Pregnancy, breastfeeding, children, older adults, and people with liver or kidney conditions are commonly excluded from trials; nothing here says whether they were.

What the label states about particular groups

  • On pediatric, the label states: “Pediatric Use Safety and effectiveness in pediatric patients have not been established.”

    US prescribing information · 81356b45-1cb7-4eef-88ea-e44cc18b47c5 · read 2026-08-30

  • On older people, the label states: “Geriatric Use A total of 13.5% (22/162) patients were 65 years of age and older and 1.2% (2/162) patients were 75 years of age and older at initiation of treatment in clinical studies for ALS in patients who have a mutation in the superoxide dismutase 1 ( SOD1 ) gene [see Clinical Studies ( 14 )] .”

    US prescribing information · 81356b45-1cb7-4eef-88ea-e44cc18b47c5 · read 2026-08-30

  • On people who are pregnant, the label states: “Pregnancy Risk Summary There are no adequate data on developmental risks associated with the use of QALSODY in pregnant women to evaluate for a drug-associated risk of major birth defects, miscarriage, or other adverse maternal or fetal outcomes.”

    US prescribing information · 81356b45-1cb7-4eef-88ea-e44cc18b47c5 · read 2026-08-30

Where the result stopped carrying

  • The pivotal clinical endpoint missed outright, and every secondary clinical endpoint with it
  • An earlier SOD1 antisense candidate, ISIS 333611, was superseded before efficacy testing
  • This is a scope explorer, not a diagnosis engine.
  • It shows who was studied so you can see whether people similar to you were included.

RNAWiki cannot tell whether a study fits you. It can show who was in it.

What it would be like to takeRead from sources, not yet reviewed

Why it might seem to do nothing

A real effect and a noticed effect are different things. These are the recorded reasons the two come apart.

It was studied in different people

The people in the studies were not much like the reader.

On this record: Which groups were under-represented in the studies has not been recorded for this substance. Pregnancy, breastfeeding, children, older adults, and people with liver or kidney conditions are commonly excluded from trials; nothing here says whether they were.

The evidence may simply be wrong

Small early studies often do not hold up.

On this record: RNAWiki has not yet published a reviewed conclusion for this use.

Other reasons RNAWiki checked and found nothing for (11)
It was studied for a different goal
The studies measured something else entirely. Nothing in this record points to this reason.
A different form was studied
The studied form is not the form on the shelf. Nothing in this record points to this reason.
There was nothing to correct
Where a level is already normal, topping it up may change nothing. Nothing in this record points to this reason.
Something else had to happen too
In the studies it was paired with training, a diet or another treatment. Nothing in this record points to this reason.
The change is too small to feel
A real change can still sit below what a person notices. Nothing in this record points to this reason.
Day-to-day swing hides it
Sleep, food, stress and time of day move most numbers more than this would. Nothing in this record points to this reason.
Not enough time yet
The studies ran longer than the person has waited. Nothing in this record points to this reason.
It was not taken as studied
Missed days change the result, and studies count them. Nothing in this record points to this reason.
Something else changed at the same time
Two changes at once cannot be told apart afterwards. Nothing in this record points to this reason.
The product may not be what it says
Contents of a sold product are not always what the label states. Nothing in this record points to this reason.
No recorded reason
RNAWiki has nothing stored that would explain it. Nothing in this record points to this reason.

None of these is a reason to take more. Taking more is not a step this page ever suggests.

What it would be like to takeRead from sources, not yet reviewed

What taking it involves

The recorded facts about getting hold of it and using it. Nothing here is a suggestion about what you should do.

How it is supplied

Not established

Quoted from a source

Where this came from

Copied from a source RNAWiki stored, with the source named.

Read from the recorded approval status.

No source is stored against this line.

Form and route

Intrathecal injection of a mixed-backbone 2-prime-MOE gapmer

Source-linked record

Where this came from

A person wrote this into the record with the study named beside it. No reviewer has signed it off.

The form and route recorded on this substance.

No source is stored against this line.

Who oversees it

Professional supervision is normally required. It is a prescription or clinician-administered medicine where it is approved.

Quoted from a source

Where this came from

Copied from a source RNAWiki stored, with the source named.

The identity record classes it as ASO (Antisense Oligonucleotide).

No source is stored against this line.

What is in the pack

Preservative-free solution given by lumbar puncture, three loading doses at 14-day intervals and then monthly. No carrier and no ligand; the phosphorothioate content alone drives cellular uptake.

Source-linked record

Where this came from

A person wrote this into the record with the study named beside it. No reviewer has signed it off.

Recorded notes on how this is sold and what that means for what is in the pack.

No source is stored against this line.

Where it is registered

Regulatory records are listed in the technical disclosure at the foot of this page.

Counted from records

Where this came from

A count of rows RNAWiki holds. It describes our records, not your body.

Register entries are stored per jurisdiction and shown with their dates.

No source is stored against this line.

Why people stop

Not recorded.

Nothing recorded

Where this came from

RNAWiki holds nothing here and says so rather than guessing.

No record of why people stopped taking it is stored for this substance.

No source is stored against this line.

What it would be like to takeRead from sources, not yet reviewed

What can go wrong

Sorted by where each line came from. A regulator's label and a report somebody sent in are not the same kind of fact.

Worth asking a clinician aboutWritten into the record from the studies named on this page

Warnings for myelitis and radiculitis, papilledema with elevated intracranial pressure, and aseptic meningitis. Neurologic serious adverse events in 7 percent of recipients. Common reactions include pain, fatigue, arthralgia, raised cerebrospinal fluid white cell count and myalgia.

Nobody counted how many people took this and were fine, so this cannot be turned into a rate.

Where this came from

Over a long time. No completed tested study window is recorded, so long-term effects are not established by the registry record.

Groups the studies covered thinly. Which groups were under-represented in the studies has not been recorded for this substance. Pregnancy, breastfeeding, children, older adults, and people with liver or kidney conditions are commonly excluded from trials; nothing here says whether they were.

What is missing or unclearRead from sources, not yet reviewed

Does the exact form matter?

Evidence belongs to the exact thing that was tested. A different salt, a different mixture or a different preparation is a different question.

The form that was studied

Intrathecal injection of a mixed-backbone 2-prime-MOE gapmer

Source-linked record

Where this came from

A person wrote this into the record with the study named beside it. No reviewer has signed it off.

The form used in the studies cited on this page.

No source is stored against this line.

What is sold

No carrier and no ligand; the phosphorothioate content alone drives cellular uptake.

Source-linked record

Where this came from

A person wrote this into the record with the study named beside it. No reviewer has signed it off.

Recorded notes on which forms are sold and how they compare.

No source is stored against this line.

What is recorded as being sold

  • 1 product lists this as an active ingredient in the United States drug directory. 1 of them contain it and nothing else.

    FDA National Drug Code directory · 64406-109 · read 2026-08-29

  • They are sold as injection, taken intrathecal.

    FDA National Drug Code directory · 64406-109 · read 2026-08-29

  • The regulator's established pharmacologic class for it is antisense oligonucleotide [epc], antisense [cs] and oligonucleotides.

    FDA National Drug Code directory · 64406-109 · read 2026-08-29

  • 1 published label names it as an active ingredient. 1 of them describe this substance alone, which is where its own label text on this page comes from.

    US prescribing information · 81356b45-1cb7-4eef-88ea-e44cc18b47c5 · read 2026-08-29

  • Those labels are classed as human prescription drug.

    US prescribing information · 81356b45-1cb7-4eef-88ea-e44cc18b47c5 · read 2026-08-29

  • QALSODY is intrathecal at 3 DOSAGE FORMS AND STRENGTHS Injection: 100 mg/15 mL (6.7 mg/mL) as a clear and colorless to slightly yellow solution in a single-dose vial., recorded as fda label in effect 2024-11-13 in the United States.

    US prescribing information · 81356b45-1cb7-4eef-88ea-e44cc18b47c5 · read 2026-08-30

Evidence carries across two names for one substance. It does not carry across a salt, a mirror form or a mixture.

What it would be like to takeRead from sources, not yet reviewed

What you could measure

This one is decided with a clinician, so this section holds questions to ask rather than a plan to run.

Self-experiment planning is not offered for a prescription or clinician-supervised medicine. The questions below are for a clinician or pharmacist.

Questions worth asking

  • Which of the trials of Tofersen studied people like me?
  • What was measured, and for how long?
  • Was the result a laboratory value or a health outcome?
  • What would we watch for, and when would we stop?

Tracking can show whether something changed for you. It cannot show what caused it.

RNAWiki records evidence. It does not say whether this substance is right for you.

What is missing or unclearRead from sources, not yet reviewed

Claims that go past the evidence

Things said about this substance that sound reasonable, and the exact step that is missing between the evidence and the claim.

Goes past the evidence

That falling neurofilament light chain predicts preserved function or survival in SOD1-ALS

Why it sounds right. It follows from something real on this page: a body step, an animal result or a related finding.

The missing step. Nobody measured this in people for this use, or the study that did measure it did not show it.

What would change this

A study in people, for this exact use, measuring this exact thing, that a reviewer signs off.

RNAWiki has not yet published a reviewed conclusion for this use.

Goes past the evidence

That the open-label delayed-start difference of 3.5 points is a randomised treatment effect

Why it sounds right. It follows from something real on this page: a body step, an animal result or a related finding.

The missing step. Nobody measured this in people for this use, or the study that did measure it did not show it.

What would change this

A study in people, for this exact use, measuring this exact thing, that a reviewer signs off.

RNAWiki has not yet published a reviewed conclusion for this use.

Goes past the evidence

That the result generalises to non-SOD1 ALS, which is about 98 percent of cases

Why it sounds right. It follows from something real on this page: a body step, an animal result or a related finding.

The missing step. Nobody measured this in people for this use, or the study that did measure it did not show it.

What would change this

A study in people, for this exact use, measuring this exact thing, that a reviewer signs off.

RNAWiki has not yet published a reviewed conclusion for this use.

What is missing or unclearRead from sources, not yet reviewed

What nobody knows yet

Open questions, each with why it is open and what would close it.

How much did people take in the studies?

The sources RNAWiki checked hold nothing for this field.

Why it matters. A result belongs to an amount. Without the amount the result floats free.

What would answer it

A stored source that records it, and a reviewer to sign it off.

Last checked 2026-09-04. Searched: The sources listed in the receipts at the foot of this page.

Missing populations

Which groups were under-represented in the studies has not been recorded.

Why it matters. Recorded by the evidence model as a gap on this record.

What would answer it

A study that measures it, and a reviewer to sign it off.

Last checked 2026-09-04. Searched: The sources listed in the receipts at the foot of this page.

Missing long-term data

No completed tested study window is recorded.

Why it matters. Recorded by the evidence model as a gap on this record.

What would answer it

A study that measures it, and a reviewer to sign it off.

Last checked 2026-09-04. Searched: The sources listed in the receipts at the foot of this page.

No reviewed conclusion

RNAWiki has not yet published a reviewed conclusion for this use.

Why it matters. Recorded by the evidence model as a gap on this record.

What would answer it

A study that measures it, and a reviewer to sign it off.

Last checked 2026-09-04. Searched: The sources listed in the receipts at the foot of this page.

Missing interaction studies

No interaction was found in the registers checked. Not finding one is not the same as showing there is none.

Why it matters. Recorded by the evidence model as a gap on this record.

What would answer it

A study that measures it, and a reviewer to sign it off.

Last checked 2026-09-04. Searched: The sources listed in the receipts at the foot of this page.

Formulation uncertainty

Several salts, forms or products of Tofersen are recorded. Results from one form may not transfer to another.

Why it matters. Recorded by the evidence model as a gap on this record.

What would answer it

A study that measures it, and a reviewer to sign it off.

Last checked 2026-09-04. Searched: The sources listed in the receipts at the foot of this page.

Mechanism not reviewed

No reviewed mechanism story exists for this substance.

Why it matters. Recorded by the evidence model as a gap on this record.

What would answer it

A study that measures it, and a reviewer to sign it off.

Last checked 2026-09-04. Searched: The sources listed in the receipts at the foot of this page.

What happened in peopleRead from sources, not yet reviewed

Check any of this yourself

Every line above traced back to the study it came from. This is the technical layer, and the vocabulary changes here.

Every line above can be traced to the study named beside it. Follow the link and read it.

The clinical primary endpoint missed, with a p-value of 0.97
In plain words
In the pivotal trial, treated patients declined on the ALS functional scale essentially as fast as patients on placebo.
What was measured
ALSFRS-R difference at week 28: 1.2 points, 95 percent CI -3.2 to 5.5, p=0.97
Effect estimate
No reviewed effect estimate exists for this record.
Limits
This entry records a failure.
From the source
VALOR (NCT02623699) Part C randomised 108 adults 2:1. In the faster-progression subgroup that formed the primary analysis, change in ALSFRS-R from baseline to week 28 was -6.98 with tofersen and -8.14 with placebo, a difference of 1.2 points (95 percent CI -3.2 to 5.5), p=0.97. Secondary clinical endpoints including slow vital capacity and handheld dynamometry also did not differ significantly.
Source
Miller et al., New England Journal of Medicine 2022 (VALOR)
Role in the trial
Not matched to a registered study
Identity check
no open identity hold
Audit mark
verified
Review state
Written into the record, not signed off as a reviewed claim
Plasma neurofilament light chain fell 55 percent
In plain words
A blood marker released when nerve fibres break down dropped by more than half in treated patients and rose in the placebo group.
What was measured
Plasma NfL: -55 percent with tofersen versus +12 percent with placebo, p<0.0001
Effect estimate
No reviewed effect estimate exists for this record.
Limits
See the technical detail.
From the source
At week 28 plasma neurofilament light chain showed a 55 percent reduction with tofersen against a 12 percent increase with placebo, p<0.0001. This, not any clinical measure, is the basis on which accelerated approval was granted. SOD1 protein in cerebrospinal fluid also fell, confirming target engagement.
Source
QALSODY US prescribing information, sections 1 and 14
Role in the trial
Not matched to a registered study
Identity check
no open identity hold
Audit mark
verified
Review state
Written into the record, not signed off as a reviewed claim
Neurofilament is a marker of damage, not a measure of how a patient is
In plain words
Falling neurofilament means fewer nerve fibres are breaking down right now. It does not tell you whether someone will keep walking, swallowing or breathing.
What was measured
That a 55 percent reduction in plasma neurofilament light chain slows ALS
Effect estimate
No reviewed effect estimate exists for this record.
Limits
See the technical detail.
From the source
The label states in plain terms that the indication is approved under accelerated approval based on reduction in plasma neurofilament light chain, and that continued approval may be contingent on verification of clinical benefit in confirmatory trials. In the same trial in which neurofilament fell 55 percent, the functional scale did not separate at all. The surrogate and the outcome pointed in different directions in the same 108 patients.
Source
QALSODY US prescribing information, section 1
Role in the trial
Not matched to a registered study
Identity check
no open identity hold
Audit mark
contested
Review state
Written into the record, not signed off as a reviewed claim
The failure was reinterpreted as "treated too late"
In plain words
When the trial missed, the field concluded the drug was given too late rather than that it does not work, and a new trial now starts treatment before symptoms appear.
What was measured
That earlier initiation would have produced a positive primary endpoint; the delayed-start comparison is not randomised evidence for that
Effect estimate
No reviewed effect estimate exists for this record.
Limits
See the technical detail.
From the source
In the combined analysis of the randomised phase and its open-label extension at 52 weeks, ALSFRS-R change was -6.0 in the early-start cohort against -9.5 in the delayed-start cohort, a difference of 3.5 points (95 percent CI 0.4 to 6.7). These comparisons were not adjusted for multiplicity and the cohorts were not randomised to their start times. That result, plus the neurofilament data, motivated ATLAS (NCT04856982), the first interventional trial in presymptomatic ALS, which has not yet reported.
Source
Miller et al., NEJM 2022, open-label extension analysis
Role in the trial
Not matched to a registered study
Identity check
no open identity hold
Audit mark
caution
Review state
Written into the record, not signed off as a reviewed claim
Serious neurologic adverse events in 7 percent of recipients
In plain words
Some patients developed inflammation of the spinal cord or nerve roots, raised pressure in the head, or meningitis without infection.
What was measured
Neurologic serious adverse events in 7 percent of tofersen recipients
Effect estimate
No reviewed effect estimate exists for this record.
Limits
See the technical detail.
From the source
The label carries warnings for myelitis and radiculitis, papilledema and elevated intracranial pressure, and aseptic meningitis. Neurologic serious adverse events occurred in 7 percent of tofersen recipients in the randomised phase. Common adverse reactions at 10 percent or more include pain, fatigue, arthralgia, increased cerebrospinal fluid white cell count and myalgia. Lumbar-puncture-related events were common in both arms.
Source
QALSODY US prescribing information, sections 5 and 6
Role in the trial
Not matched to a registered study
Identity check
no open identity hold
Audit mark
verified
Review state
Written into the record, not signed off as a reviewed claim
It applies to about 2 percent of people with ALS
In plain words
This is a drug for one genetic subtype. It says nothing about whether antisense will work for the other 98 percent of ALS.
What was measured
That tofersen demonstrates antisense therapy works in ALS generally
Effect estimate
No reviewed effect estimate exists for this record.
Limits
See the technical detail.
From the source
SOD1 variants account for roughly 2 percent of all ALS. Tofersen lowers SOD1 specifically and has no mechanism of action in C9orf72, TDP-43 or sporadic disease. Trials of antisense drugs against other ALS genes are separate programmes with separate evidence, and the tofersen result does not transfer to them.
Source
QALSODY US prescribing information, section 1
Role in the trial
Not matched to a registered study
Identity check
no open identity hold
Audit mark
caution
Review state
Written into the record, not signed off as a reviewed claim

Where else this substance is registered

FDA substance identifier (UNII)
2NU6F9601K
RxNorm concept
2634999

Checks this page had to pass

  • Passed

    Identity resolved

    no open identity hold

  • Passed

    No unresolved merge across substance families

    no quarantine open

  • Passed

    Every public sentence names a source

    The opening statement carries the origin: Reviewed first-read answer.

  • Not passed

    Trial roles classified for highlighted evidence

    No registered study is classified as testing this substance.

  • Passed

    No internal keys in reader text

    enforced by the copy-contract test over the rendered page

  • Passed

    Safety mode resolved

    The identity record classes it as ASO (Antisense Oligonucleotide).

  • Passed

    Canonical metadata present

    slug and display name present

What is missing or unclearRead from sources, not yet reviewed

How this medicine reached us

Kept near the foot of the page. A historical event moves up only when it changes something about this substance today.

What the approval register records

  • 1 approved application covers products containing this substance. The earliest was NDA215887, approved 20230425 to BIOGEN MA.

    Drugs@FDA application register · NDA215887 · read 2026-08-29

  • Marketing status on the register: prescription.

    Drugs@FDA application register · NDA215887 · read 2026-08-29

  • The earliest marketing start date recorded for a listed product is 20230425.

    FDA National Drug Code directory · 64406-109 · read 2026-08-29

What is missing or unclearRead from sources, not yet reviewed

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What is not here

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  • What was measured, goal by goal — found nothing in the sources checked.
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  • Felt, measured, or meaningful — found nothing in the sources checked.
  • How long anything takes — found nothing in the sources checked.
  • What it may clash with — found nothing in the sources checked.
  • Other ways to the same goal — found nothing in the sources checked.
  • What changed on this page — found nothing in the sources checked.

The record as stored

The full record, for auditing

Everything above is built from what is below. This layer keeps the technical vocabulary, record identifiers and every stored row, so a reader who wants to check the page can.

The older medicine-wide conclusion held in this record

Written for a clinical reader, and about the medicine as a whole rather than about one indication, population and set of trials. RNAWiki does not treat it as a programme conclusion and no reviewer has signed it off in that form. It is here word for word because it is what the record holds.

The first drug approved for a genetic cause of ALS, cleared on a 55 percent fall in plasma neurofilament light chain after its clinical primary endpoint missed by a wide margin (difference 1.2 points on ALSFRS-R, p=0.97).

Recorded evidence blocks (5)

On the Tofersen label: indicated for what?


"QALSODY is indicated for the treatment of amyotrophic lateral sclerosis (ALS) in adults who have a mutation in the superoxide dismutase 1 ( SOD1 ) gene. This indication is approved under accelerated approval based on reduction in plasma neurofilament light chain (NfL) observed in patients treated with QALSODY [see…": indications and usage on Tofersen's label. DailyMed label · 81356b45-1cb7-4eef-88ea-e44cc18b47c5 · 2024-11-13

8 registered trials of Tofersen — at which phases?


Registered studies posting no result
6 of 8

8 registered studies of Tofersen: 3 phase3, 2 na or unstated, 1 phase1, 1 phase2, 1 phase4. CLINICALTRIALS_SNAPSHOT · 2026-09-01

3 with a PubMed record

Show the evidence
  • phase3
    3
  • na or unstated
    2
  • phase1
    1
  • phase2
    1
  • phase4
    1
  • completed
    3
3 more recorded rows
  • active not recruiting
    2
  • recruiting
    2
  • approved for marketing
    1

recorded 2026-09-01 · last checked 2026-09-04

Tofersen's half-life is 4 weeks — which schedules were studied?


4 weeks, the half-life Tofersen's label states: "The effective half-life in CSF is estimated to be 4 weeks." DailyMed label · 81356b45-1cb7-4eef-88ea-e44cc18b47c5 · 2024-11-13

tmax 2 to 6 hours.

Show the evidence
  • half life pharmacokinetics
    4 weeks; The effective half-life in CSF is estimated to be 4 weeks.
  • tmax pharmacokinetics
    2 to 6 hours; Tofersen is transferred from CSF into the systemic circulation, with median time to maximum concentration (T max ) plasma values ranging from 2 to 6 hours.
  • metabolism pharmacokinetics
    Elimination Metabolism Tofersen is expected to be metabolized through exonuclease (3'- and 5')-mediated hydrolysis and is not a substrate for, or inhibitor or inducer of CYP450 enzymes.

recorded 2024-11-13 · last checked 2026-09-04

Which one trial of Tofersen posted no result?


Posted no result
1 of 1 completed trials
Registrations
NCT03764488
Completion dates
oldest 2021-07-10
Show the evidence
  • Trial NCT03764488
    2021-07-10

At the median, Tofersen's trials enrolled 125 people — anything larger?


Median enrolment
125
Largest enrolment
176
Registered trials counted
7
Where it is registered
Identifiers, relations and other names

The exact record

ChEMBL id
CHEMBL3833346
CAS number
2088232-70-4
RxCUI
2634999
Development code
BIIB-067, BIIB067, ISIS-SOD1Rx
Trade name
Qalsody
Also called
TOFERSEN [JAN], TOFERSEN [USAN], Tofersen [MI], Tofersen [WHO-DD], tofersen [INN]
Sources (4)

Sources

ChEMBL 37 — CC BY-SA 3.0 Unported · ChEMBL ATC CC BY-SA · ClinicalTrials.gov — US Government work · mixed register set; per-register licences in docs/specs/corpus-20k-sources.md · openFDA / DailyMed — US Government work

How these records are assembled · Which registers were checked

Index-quality checks
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  • required summary fields resolved: 4 required field(s) not terminal: Why people use it, Best-supported result, Biggest unanswered question, Human evidence
  • public claims reviewed: 0 reviewed claim(s); drafts are never rendered
  • source coverage passed: 4 source rows
  • no critical contamination: no quarantine open
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This is a record of evidence. It is not medical advice, and it does not say this substance suits you. Nothing here says any substance on RNAWiki is appropriate for a child.