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Aducanumab-avwa

  • Withdrawn substance
  • Withdrawn
  • 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 Aducanumab-avwa does in the body

Whether that slows memory loss is the part that two large trials of the same drug answered differently.

Alzheimer's brains accumulate clumps of a protein called amyloid beta. Aducanumab is an antibody that grips those clumps, which flags them for immune cells in the brain to engulf and clear. Brain scans show the clumps do shrink, substantially and in proportion to dose and time.

Why people take it. A monthly infusion for early Alzheimer's disease, approved on a brain-scan measurement rather than on symptoms

What happened in people

Dose- and time-dependent reduction of brain amyloid beta plaque on florbetapir PET

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 recorded finding that sits closest to something a person would notice. Written into the record, not signed off, and it carries no population or interval.

The limit that matters most

That amyloid plaque reduction predicts clinical benefit — this is the premise of the accelerated approval, and it is the proposition the confirmatory trial was meant to test

Where it acts
Cerebral cortex and leptomeningeal vasculature; amyloid plaque in brain parenchyma and vessel walls
Kind of result
The kind of result is not recorded
Supervision
Professional supervision is normally required. It is a prescription or clinician-administered medicine where it is approved.
Where each sentence above came from

A person wrote this explanation into the record, with the studies named in the path below.

The recorded use, written for a reader without medical training. Not signed off.

A limit recorded against this substance. Not signed off as a reviewed claim.

The four opening statements run to 92 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.

Formulation

A formulation is the exact made-up form a substance comes in.

A picture of it, and where the picture fails

It is like the difference between a whole bean and instant coffee.

Where that stops being true. Coffee tastes different. A formulation can change how much reaches the blood.

What people get wrong. Two products with the same name are assumed to behave the same. They often do not.

The specific composition and physical form of a product, including salt, excipients and release profile.

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 in Clinical Dementia Rating Sum of Boxes at week 78 in early Alzheimer's disease

The study showed what it set out to show

Who was studied
NCT02484547
How many people
1638
Study design
Phase 3 (EMERGE)
Compared against
Not recorded for this study
Kind of result
A number that stands in for health
What was found
High-dose aducanumab showed significant treatment effects across primary and secondary endpoints; low dose non-significant and intermediate
Repeated elsewhere
Failed to Replicate

What this does not prove. Meeting one endpoint in one population does not carry to other goals or other people.

The limits of this study, and where it came from

Main limit. The trial was terminated for futility in March 2019 and the positive result comes from the larger dataset assembled after that stop. Its identically designed twin did not reproduce it.

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

Form and route. Intravenous infusion every four weeks, with stepwise titration

Interval reported. Not recorded in this summary

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

Change from baseline in Clinical Dementia Rating Sum of Boxes at week 78 in early Alzheimer's disease

The study did not show it

Who was studied
NCT02477800
How many people
1647
Study design
Phase 3 (ENGAGE)
Compared against
Not recorded for this study
Kind of result
A number that stands in for health
What was found
High-dose aducanumab did not demonstrate a significant treatment effect; low-dose results consistent with EMERGE and non-significant
Repeated elsewhere
Failed to Replicate

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. The sponsor attributes the outcome to a small number of extremely rapid progressors and lower exposure to the 10 mg/kg target dose among early-enrolled patients. Both analyses are post hoc.

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

Form and route. Intravenous infusion every four weeks, with stepwise titration

Interval reported. Not recorded in this summary

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

Amyloid plaque clearance below 24.1 centiloids on florbetapir PET, donanemab versus aducanumab

The study showed what it set out to show

Who was studied
NCT05108922
How many people
148
Study design
Phase 3 open-label head-to-head (TRAILBLAZER-ALZ 4)
Compared against
Not recorded for this study
Kind of result
A number that stands in for health
What was found
Clearance at 6, 12 and 18 months: donanemab 37.9, 70.0 and 76.8 per cent versus aducanumab 1.6, 24.6 and 43.1 per cent, P < 0.001; median time to clearance 359 versus 568 days
Repeated elsewhere
Unreplicated

What this does not prove. Meeting one endpoint in one population does not carry to other goals or other people.

The limits of this study, and where it came from

Main limit. ARIA-oedema or effusion in 34.8 per cent on aducanumab and 23.9 per cent on donanemab. The study compares a biomarker only and reports no cognitive comparison.

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

Form and route. Intravenous infusion every four weeks, with stepwise titration

Interval reported. Not recorded in this summary

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

What we know
RNAWiki holds 3 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 happened in peopleRead from sources, not yet reviewed

How close this is to real life

The top step is something a person would feel or care about. The bottom is a guess from software. Filled steps are where evidence exists for this substance.

  1. Living longer, or avoiding a major event No evidence recorded. Death, a heart attack, a stroke, a hospital stay.No registered study measures this.
  2. What a body can do day to day No evidence recorded. Walking, dressing, breathing, recovering.No registered study measures this.
  3. Measured performance No evidence recorded. How much was lifted, how far was run, how fast.No registered study measures this.
  4. Symptoms and quality of life No evidence recorded. Pain, tiredness, mood, sleep, as the person rated it.No registered study measures this.
  5. A number that stands in for health No evidence recorded. Cholesterol, blood sugar, bone density. A stand-in, not the thing itself.No registered study measures this.
  6. A step measured inside a person Evidence recorded. Something measured in human tissue or human cells.A human record sits on the stored organism ladder.
  7. Animals No evidence recorded. Mice, rats, dogs. Useful for ideas, not proof about people.No animal record is stored.
  8. Cells in a dish No evidence recorded. Cells or chemistry on a bench, far from a whole body.No cell or bench record is stored.
  9. A guess from software No evidence recorded. Nobody measured it. RNAWiki never publishes one as a finding.RNAWiki stores no prediction for this record. Software can suggest a link. RNAWiki does not publish one as a finding.

Higher on these steps means closer to something a person would feel. It does not mean better done.

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

    Aducanumab-avwa

    What a person takes: Intravenous infusion every four weeks, with stepwise titration.

    The measurement behind this step

    One-hour intravenous infusion every four weeks, titrated over several months to a 10 mg/kg target dose. Serial MRI surveillance for amyloid-related imaging abnormalities is required throughout, and APOE genotype stratifies that risk.

  2. Getting in

    A monthly intravenous infusion, titrated up over months

    Given as a drip once a month, starting low and increasing in steps to the target dose.

    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

    Intravenous infusion every four weeks with stepwise titration to a 10 mg/kg target. The titration exists to limit amyloid-related imaging abnormalities, and under-exposure to the target dose during titration is one of the factors invoked to explain the ENGAGE result.

  3. Reaching the cell

    A small fraction crosses into the brain

    Most of an antibody this size stays in the bloodstream; only a small percentage reaches brain tissue.

    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

    IgG penetration of the intact blood-brain barrier is on the order of a fraction of a per cent of plasma concentration, which is why the doses are large relative to the target burden.

  4. What it acts on

    Binds aggregated amyloid, not monomer

    It grips the clumped form of the protein and largely ignores the free-floating single molecules.

    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

    Binds a linear N-terminal epitope of amyloid beta with strong conformational selectivity for fibrils and oligomers over monomer, concentrating the antibody on parenchymal plaque and on cerebral amyloid angiopathy in vessel walls.

  5. The change it makes

    Microglia clear the flagged plaque

    The brain's resident immune cells recognise the antibody coating and engulf the plaque. Vessel-wall involvement is what produces the swelling seen on scans.

    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

    Fc-gamma receptor engagement on microglia drives phagocytosis of opsonised plaque. The same process at perivascular amyloid increases vessel permeability, producing ARIA-oedema, and vessel-wall fragility, producing ARIA-haemosiderin.

  6. What that does for a person

    Plaque falls in every study; cognition slowed in one trial of two

    Amyloid on the scan drops reliably. Whether thinking and memory decline more slowly was answered yes by one trial and no by its twin.

    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

    Measured: plaque clearance in 43.1 per cent at 18 months in the head-to-head study. Measured: EMERGE high dose significant on primary and secondary endpoints, ENGAGE high dose not, with low-dose arms consistent and non-significant in both. ARIA-oedema in 34.8 per cent.

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.

  • Nobody. Biogen discontinued the product in 2024 and stopped the confirmatory trial. Patients were transitioned to lecanemab or donanemab, later anti-amyloid antibodies with completed phase 3 programmes.

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.

Where the result stopped carrying

  • Both phase 3 trials were terminated for futility in March 2019
  • ENGAGE high dose did not reproduce the EMERGE high-dose result under an identical protocol
  • The advisory committee opposed approval and three members resigned after it was granted
  • Biogen discontinued the product and the confirmatory trial in January 2024, so the deferred question was never answered
  • 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 for a different goal

The studies measured something else entirely.

On this record: Some registered studies measured things that match no goal on this page.

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.

A different form was studied

The studied form is not the form on the shelf.

On this record: This record is linked to 1 related forms. Evidence does not carry across all of them.

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 (9)
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

Withdrawn

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

Intravenous infusion every four weeks, with stepwise titration

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.

A register records the withdrawal of an approval.

No source is stored against this line.

What is in the pack

One-hour intravenous infusion every four weeks, titrated over several months to a 10 mg/kg target dose. Serial MRI surveillance for amyloid-related imaging abnormalities is required throughout, and APOE genotype stratifies that risk.

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

Amyloid-related imaging abnormalities are the principal harm: oedema or effusion in 34.8 per cent of aducanumab-treated participants in a randomised head-to-head study, alongside microhaemorrhage and superficial siderosis. Most ARIA is asymptomatic and detected on scheduled imaging, but symptomatic and serious cases occur, and risk is higher in APOE4 carriers. Headache, falls, diarrhoea and confusion were reported. The product was discontinued by its sponsor in January 2024.

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

Intravenous infusion every four weeks, with stepwise titration

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

Serial MRI surveillance for amyloid-related imaging abnormalities is required throughout, and APOE genotype stratifies that risk.

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.

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

Names and forms linked to this record

  • Biosimilar of

    Aducanumab

    Evidence on this page does not automatically apply to this one.

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, withdrawn medicine. The questions below are for a clinician or pharmacist.

Questions worth asking

  • Which of the trials of Aducanumab-avwa 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 amyloid plaque reduction predicts clinical benefit — this is the premise of the accelerated approval, and it is the proposition the confirmatory trial was meant to test

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 post-hoc identification of rapid progressors and under-dosing in ENGAGE establishes EMERGE as the correct result

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 faster plaque clearance by a competitor implies greater clinical benefit; the head-to-head study measured no cognitive endpoint

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.

How fast does the body clear it?

The sources RNAWiki checked hold nothing for this field.

Why it matters. Without this, nothing on this page can say how long anything lasts.

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 Aducanumab-avwa 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.

Amyloid plaque fell, and the measurement is sound
In plain words
Brain scans showed the drug removes amyloid plaque in a dose- and time-dependent way. That part is not in dispute.
What was measured
Brain amyloid beta plaque burden on florbetapir PET, dose- and time-dependent reduction
Effect estimate
No reviewed effect estimate exists for this record.
Limits
See the technical detail.
From the source
The phase 1b PRIME study established dose- and time-dependent reduction of brain amyloid beta plaque on florbetapir PET in patients with prodromal or mild Alzheimer's disease, with the fully human antibody selected for selectivity toward aggregated over monomeric amyloid. In the later head-to-head TRAILBLAZER-ALZ 4 study, amyloid plaque clearance — defined as below 24.1 centiloids — was achieved by 1.6 per cent, 24.6 per cent and 43.1 per cent of aducanumab-treated participants at 6, 12 and 18 months. The surrogate endpoint behaves exactly as claimed. The question the approval turned on is what it predicts.
Source
Sevigny J et al. Nature 2016;537:50-56; Salloway S et al. Alzheimers Dement 2025;21:e70293
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
Two identical trials, opposite answers, and a futility stop in between
In plain words
Two trials of the same drug, run at the same time to the same protocol, were stopped early for futility in March 2019. Later analysis of more data made one of them positive and left the other negative.
What was measured
Not recorded
Effect estimate
No reviewed effect estimate exists for this record.
Limits
See the technical detail.
From the source
EMERGE (NCT02484547) and ENGAGE (NCT02477800) were two phase 3 randomised double-blind placebo-controlled parallel-group studies at 348 sites in 20 countries, enrolling patients aged 50 to 85 with mild cognitive impairment or mild Alzheimer's dementia and confirmed amyloid pathology, randomised 1:1:1 to low-dose aducanumab, high-dose aducanumab or placebo every four weeks. The randomised and dosed populations were 1,638 in EMERGE and 1,647 in ENGAGE. Both were terminated for futility in March 2019. On the larger dataset available afterwards, high-dose aducanumab in EMERGE showed significant treatment effects across primary and secondary endpoints, and high-dose aducanumab in ENGAGE did not. Low-dose results were consistent across both studies, non-significant, and intermediate to the EMERGE high-dose arm.
Source
Budd Haeberlein S et al. J Prev Alzheimers Dis 2022;9:197-210; Mallinckrodt C et al. J Prev Alzheimers Dis 2023;10:171-177
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 reconciliation of the two trials is post hoc
In plain words
The sponsor's explanation for why one trial worked and the other did not was worked out after the results were known, by looking for differences that could account for the gap.
What was measured
That the post-hoc identification of rapid progressors and under-dosing in ENGAGE establishes EMERGE as the correct result
Effect estimate
No reviewed effect estimate exists for this record.
Limits
See the technical detail.
From the source
The published reconciliation examined four candidate explanations — baseline characteristics, amyloid-related imaging abnormalities, non-normality of the data, and dosing exposure — and concluded that ENGAGE high-dose outcomes were affected by an imbalance in a small number of patients with extremely rapid progression and by lower exposure to the 10 mg/kg target dose, factors that were confounded with each other and concentrated among early-enrolled patients. Baseline characteristics and ARIA were excluded as contributors. Every one of these analyses is post hoc, performed on unblinded data with the discordance already known. Post-hoc reconciliation is a legitimate way to generate a hypothesis for the next trial. It is not a replacement for the trial that would test it, and that trial was never completed.
Source
Mallinckrodt C et al. J Prev Alzheimers Dis 2023;10:171-177
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
Approved against the unified opposition of its own advisory committee
In plain words
The FDA's external expert committee did not support approval. The agency approved the drug anyway, on the amyloid measurement rather than on the cognitive results.
What was measured
Not recorded
Effect estimate
No reviewed effect estimate exists for this record.
Limits
See the technical detail.
From the source
Accelerated approval was granted in June 2021 on reduction of amyloid beta plaque as a surrogate reasonably likely to predict clinical benefit, despite the unified opposition of the agency's advisory committee following the early termination of the two efficacy trials. Three members of the Peripheral and Central Nervous System Drugs Advisory Committee resigned afterwards. The published critique frames the central issue precisely: accelerating approval on a surrogate marker in the absence of proven efficacy creates a risk of adverse outcomes even in a devastating condition. The disagreement is not about whether amyloid fell. It is about whether a measurement that reliably tracks the drug's pharmacology reliably tracks the patient's future.
Source
Rizk JG, Lewin JC. BMJ Evid Based Med 2023;28:78-82
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
ARIA is common, and it is measurable
In plain words
Brain swelling or small bleeds visible on MRI occurred in about a third of treated patients in the head-to-head comparison. It is monitored with scheduled scans.
What was measured
Incidence of amyloid-related imaging abnormalities, oedema and effusion type, in a randomised head-to-head study
Effect estimate
No reviewed effect estimate exists for this record.
Limits
See the technical detail.
From the source
Amyloid-related imaging abnormalities of the oedema and effusion type occurred in 34.8 per cent of aducanumab-treated participants in the randomised head-to-head study against donanemab, in which the donanemab figure was 23.9 per cent. ARIA is detected by scheduled MRI rather than by symptoms, is more frequent in APOE4 carriers, and is the reason the whole anti-amyloid class carries a surveillance imaging schedule. It is a genuinely quantified harm with a defined grading scale, which distinguishes it from the efficacy question on the same drug.
Source
Salloway S et al. Alzheimers Dement 2025;21:e70293
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
Discontinued in 2024 with the confirmatory trial unfinished
In plain words
Biogen stopped selling the drug and stopped the trial that was supposed to confirm whether it works. The confirming evidence was never produced.
What was measured
Not recorded
Effect estimate
No reviewed effect estimate exists for this record.
Limits
This entry records a failure.
From the source
Accelerated approval is granted on the condition that a confirmatory trial verifies clinical benefit. Biogen announced in January 2024 that it was discontinuing the product and the confirmatory study, and reallocating resources to lecanemab. The consequence is that the question the accelerated approval deferred — does removing amyloid slow the disease — was not answered by this drug. Coverage had already been constrained: the Centers for Medicare and Medicaid Services issued a national coverage determination in April 2022 limiting reimbursement for anti-amyloid monoclonal antibodies approved on the amyloid surrogate to patients enrolled in qualifying clinical studies, which effectively ended routine use.
Source
Drugs@FDA BLA 761178 (ADUHELM, Biogen); Rizk JG, Lewin JC. BMJ Evid Based Med 2023;28:78-82
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
A head-to-head comparison settled the surrogate and not the endpoint
In plain words
A later trial showed a competitor cleared amyloid faster and more completely. It did not show that the competitor helped patients more.
What was measured
That superior amyloid plaque clearance in a head-to-head study implies superior clinical benefit
Effect estimate
No reviewed effect estimate exists for this record.
Limits
See the technical detail.
From the source
TRAILBLAZER-ALZ 4 (NCT05108922) randomised 148 participants with early symptomatic Alzheimer's disease 1:1 to donanemab or aducanumab per label, with amyloid plaque clearance below 24.1 centiloids as the endpoint. Donanemab cleared plaque in 37.9, 70.0 and 76.8 per cent at 6, 12 and 18 months against 1.6, 24.6 and 43.1 per cent for aducanumab (P < 0.001), with median time to clearance 359 versus 568 days. This is a clean comparison of two drugs on a biomarker. It contains no cognitive comparison and cannot be read as evidence that either drug helps patients more than the other — which is the same category error the aducanumab approval turned on, appearing again in the literature that followed it.
Source
Salloway S et al. Alzheimers Dement 2025;21:e70293
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

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  • 1 approved application covers products containing this substance. The earliest was BLA761178, approved 20210607 to BIOGEN INC.

    Drugs@FDA application register · BLA761178 · read 2026-08-29

  • Marketing status on the register: prescription.

    Drugs@FDA application register · BLA761178 · read 2026-08-29

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An anti-amyloid antibody approved on plaque clearance after two identically designed phase 3 trials disagreed — high-dose aducanumab slowed decline on the Clinical Dementia Rating Sum of Boxes by 22 per cent in EMERGE and by nothing at all in ENGAGE — and discontinued by its sponsor in January 2024 with the confirmatory trial unfinished.

Recorded evidence blocks (8)

What did Aducanumab-avwa's largest trial (1696 people) and its longest (7 years) measure?


1696 people in Aducanumab-avwa's largest registered study, 7 years in its longest registered window, measuring PK parameter of IV dose of aducanumab: Area under the concentration-time curve from time zero to infinity (AUCinf). ClinicalTrials.gov · 2026-09-01

4 phase1, 2 phase3, 1 early phase1, 1 phase2; NCT05469009; 2029-07; no ageing endpoint recorded. Last human test completed 2022, NCT05216887.

Interpretation These counts include studies where Aducanumab-avwa was a comparison treatment, a background treatment or an exposure in an observational study, and the longest window may be a planned end date. Trial roles have not yet been classified for this record.

Show the evidence
  • phase1
    4
  • phase3
    2
  • early phase1
    1
  • phase2
    1
  • Last recorded human test NCT05216887
    2022-07-27

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

Aducanumab-avwa was tested only in human — what did it show?


human: biomarker (8): the rungs where Aducanumab-avwa has a recorded finding. Europe PMC and ClinicalTrials.gov · organism ladder · 2026-09-01

Interpretation PK parameter of IV dose of aducanumab: Area under the concentration-time curve from time zero to infinity (AUCinf) — the recorded outcome words.

Yeast C. elegans Drosophila Mouse Rat Dog Non-human primate Human biomarker
Show the evidence
  • human NCT02782975
    biomarker; PK parameter of IV dose of aducanumab: Area under the concentration-time curve from time zero to infinity (AUCinf); 8

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

3 of Aducanumab-avwa's trials stopped: safety, sponsor decision unspecified?


safety (1) and sponsor decision unspecified (2): Aducanumab-avwa's stop wording, clustered. ClinicalTrials.gov · 2026-09-01

"Study was discontinued based on futility analysis conducted on Phase 3 trials (NCT02477800 and NCT02484547) and not based on safety concerns."; 3 of 8 registered studies

Show the evidence

Trial

  • NCT03639987
    terminated; "Study was discontinued based on futility analysis conducted on Phase 3 trials (NCT02477800 and NCT02484547) and not based on safety concerns."
  • NCT04241068
    terminated; "Sponsor's Decision"
  • NCT05310071
    terminated; "Sponsor's Decision"

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

Could one person measure Aducanumab-avwa's effect on adverse events as a measure of safety and tolerability?


Adverse events as a measure of safety and tolerability: measured in Aducanumab-avwa's trials.

Interpretation adverse events as a measure of safety and tolerability is the recorded endpoint.

Show the evidence

biomarkers

  • adverse events as a measure of safety and tolerability; 2026-09-01
  • treatment intervention related adverse events; 2026-09-01
  • treatment intervention related serious adverse events; 2026-09-01
  • human trials at or under30
    3
  • Not recorded for this substance
    a recorded half-life
  • smallest human trial
    15; NCT05469009; EARLY_PHASE1; the smallest recorded human enrolment at or below 30; the registry states no direction of its result; ACTIVE_NOT_RECRUITING

Which of adverse events as a measure of safety and tolerability, treatment intervention related adverse events and treatment intervention related serious adverse events did Aducanumab-avwa's trials measure?


adverse events as a measure of safety and tolerability, treatment intervention related adverse events and treatment intervention related serious adverse events lead 3 outcome terms across Aducanumab-avwa's trials. ClinicalTrials.gov · 2026-09-01

3 terms in all.

Show the evidence
  • adverse events as a measure of safety and tolerability
    1
  • treatment intervention related adverse events
    1
  • treatment intervention related serious adverse events
    1

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

What will the one ongoing trial of Aducanumab-avwa report, and when?


1 registered trial of Aducanumab-avwa is open; earliest completion 2029-07. ClinicalTrials.gov · 2026-09-01

Interpretation Treatment intervention related adverse events

Show the evidence
  • Trial NCT05469009
    "Safety and Feasibility of Exablate Blood-Brain Barrier Disruption for Mild Cognitive Impairment or Mild Alzheimer's Disease Undergoing Standard of Care Monoclonal Antibody (mAb) Therapy"; n 15; "Treatment intervention related adverse events"; 2029-07

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

Which 4 trials of Aducanumab-avwa posted no result?


Posted no result
4 of 4 completed trials
Registrations
NCT01397539, NCT02782975, NCT04924140 and NCT05216887
Completion dates
oldest 2013-08; newest 2022-07-27
Show the evidence

Trial

  • NCT01397539
    2013-08
  • NCT02782975
    2016-11
  • NCT04924140
    2021-10-01
  • NCT05216887
    2022-07-27

At the median, Aducanumab-avwa's trials enrolled 52.5 people — anything larger?


Median enrolment
52.5
Largest enrolment
1696
Registered trials counted
8
Where it is registered
Identifiers, relations and other names

The exact record

CAS number
1384260-65-4
RxCUI
2557217

Relations

Trade name
Aduhelm
Also called
ADUCANUMAB, ADUCANUMAB [JAN], ADUCANUMAB [USAN], Aducanumab [MI], Aducanumab [WHO-DD], Aducanumab avwa [WHO-DD], IMMUNOGLOBULIN G1, ANTI-(HUMAN .BETA.-AMYLOID) (HUMAN MONOCLONAL BIIB037 HEAVY CHAIN), DISULFIDE WITH HUMAN MONOCLONAL BIIB037 .KAPPA.-CHAIN, DIMER, aducanumab [INN]
Development code
BIIB-037, BIIB037
Sources (4)

Sources

ClinicalTrials.gov — US Government work · Europe PMC — metadata only, under the recorded legal gate · derived from this page's own recorded fields; no external licence · mixed register set; per-register licences in docs/specs/corpus-20k-sources.md

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