This page shows what was measured, who it was measured in, and what that does not settle.
What Andexanet alfa does in the body
Emergency reversal of apixaban or rivaroxaban during uncontrolled bleeding.
Apixaban and rivaroxaban work by jamming an enzyme called factor Xa. Andexanet alfa is a copy of that same enzyme with two deliberate breaks: the part that does the cutting is disabled, and the part that anchors it into the clotting machinery has been cut off. So it cannot clot your blood and it cannot thin it. What it can still do is look exactly like the enzyme the drug is hunting for, so the drug binds to the decoy instead and is taken out of circulation.
What happened in people
It controlled brain bleeding more often than usual care, but did not improve disability or death at 30 days.
✓ 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
Better bleeding control did not translate into better recovery or survival.
Where it acts
Blood plasma — the decoy circulates and captures the drug before it reaches real factor Xa
Kind of result
Living longer, or avoiding a major event
Supervision
Professional supervision is normally required. A regulator classifies this substance in a way that restricts how it is supplied.
What the registries record it as
The substance registry classes this as protein.
FDA substance registry · BI009E452R · read 2026-08-29
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 117 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.
Comparator
A comparator is whatever the treatment was measured against.
A picture of it, and where the picture fails
It is like the other runner in a race.
Where that stops being true. A race has one winner. A study can show both arms improved.
What people get wrong. Results are read without asking what the other group got. Beating nothing is not beating a treatment.
The control condition against which the experimental intervention is assessed.
Randomisation
Randomisation means chance decides who gets which treatment.
A picture of it, and where the picture fails
It is like a coin toss deciding the groups.
Where that stops being true. A coin toss is fair once. Fairness here comes from doing it for everyone.
What people get wrong. It is thought to make groups identical. It makes them similar on average, including on things nobody measured.
Allocation of participants to arms by a chance process, so that unmeasured factors are balanced in expectation.
Absolute difference
An absolute difference is how many more people in a hundred were affected.
A picture of it, and where the picture fails
It is like counting heads in two rooms of a hundred.
Where that stops being true. Heads are easy to count. Study results carry a margin of error too.
What people get wrong. It is confused with a percentage change, which can look far larger.
The arithmetic difference in event rates between arms.
Confidence interval
A confidence interval is the range the true answer is likely to sit in.
A picture of it, and where the picture fails
It is like a weather forecast giving a range rather than one number.
Where that stops being true. A forecast range covers tomorrow. This one covers what the study could resolve.
What people get wrong. The middle number is read as the answer. A range crossing zero means no change is still possible.
An interval estimate that would contain the true parameter in a stated proportion of repeated studies.
What happened in people◇Read 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.
Composite haemostatic efficacy at 12 hours: haematoma expansion 35% or less, NIH Stroke Scale increase under 7 points, and no rescue therapy between 3 and 12 hours
✓ The study showed what it set out to show
Who was studied
ANNEXA-I (NCT03661528) — andexanet versus usual care in intracerebral haemorrhage
How many people
530
Study design
Phase 4 randomised open-label trial, stopped early at a positive interim analysis
Compared against
Not recorded for this study
Kind of result
A number that stands in for health
What was found
67.0% versus 53.1%, adjusted difference 13.4 percentage points (95% CI 4.6 to 22.2), p = 0.003
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. Thrombotic events 10.3% versus 5.6% (p=0.048) and ischaemic stroke 6.5% versus 1.5%. No appreciable difference in modified Rankin scale or 30-day death. Efficacy was judged on an interim analysis of 452 of the 530 patients, and the trial was stopped early.
How far it carries. This study is recorded from the curated record, not from the registry match.
Form and route. Intravenous bolus followed by a continuous infusion, given once in an emergency setting
Interval reported. 95% CI 4
Written into the record, not signed off as a reviewed claim.
Co-primary: change in anti-factor-Xa activity from baseline during treatment, and adjudicated excellent or good haemostatic efficacy at 12 hours
✓ The study showed what it set out to show
Who was studied
ANNEXA-4 (NCT02329327) — final study report
How many people
479
Study design
Phase 3b/4 multicentre prospective single-group cohort study, no control arm
Compared against
Not recorded for this study
Kind of result
A number that stands in for health
What was found
Anti-factor-Xa reduction 93% (95% CI 94 to 93) for apixaban and 94% (95% CI 95 to 93) for rivaroxaban; excellent or good haemostasis in 274 of 342 evaluable patients, 80% (95% CI 75 to 84)
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. Thrombotic events in 50 of 479 (10%). Among the 419 apixaban or rivaroxaban patients in the label safety population there were 75 deaths (18%), all before day 45. With no control group these figures have no comparator.
How far it carries. This study is recorded from the curated record, not from the registry match.
Form and route. Intravenous bolus followed by a continuous infusion, given once in an emergency setting
Interval reported. 95% CI 94 to 93) for apixaban and 94% (95% CI 95 to 93) for rivaroxaban; excellent or good haemostasis in 274 of 342 evaluable patients, 80% (95% CI 75 to 84)
Written into the record, not signed off as a reviewed claim.
ANNEXA-A (NCT02207725) bolus phase — the healthy-volunteer basis for accelerated approval
How many people
33
Study design
Two-part randomised placebo-controlled study in healthy older volunteers
Compared against
A dummy treatment
Kind of result
A number that stands in for health
What was found
Anti-factor-Xa activity reduced by 94% on andexanet against 21% on placebo (p<0.001); thrombin generation fully restored in 100% against 11% of participants within 2 to 5 minutes
Repeated elsewhere
Partially Replicated
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. Transient increases in d-dimer and prothrombin fragments 1 and 2 were observed in a subgroup, resolving within 24 to 72 hours. Participants were healthy older volunteers who were not bleeding and had no indication for anticoagulation. The companion rivaroxaban study ANNEXA-R (NCT02220725) reported a 92% reduction against 18% in its 41 bolus participants.
How far it carries. This study is recorded from the curated record, not from the registry match.
Form and route. Intravenous bolus followed by a continuous infusion, given once in an emergency setting
Interval reported. Not recorded in this summary
Written into the record, not signed off as a reviewed claim.
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 it changes in the body◇Read 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.
Start
Andexanet alfa
What a person takes: Intravenous bolus followed by a continuous infusion, given once in an emergency setting.
The measurement behind this step
Supplied as 200 mg lyophilised single-dose vials, reconstituted with sterile water for injection and given as an initial bolus followed by a continuous infusion. There is no other route and no repeat course: the drug is given during the acute bleed and stopped.
Getting in
A bolus followed by an infusion, because the decoy runs out
Given straight into a vein as an initial dose and then a continuous drip. The drip exists because the decoy is cleared quickly while the anticoagulant is still being absorbed from the gut.
──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
Supplied as 200 mg lyophilised single-dose vials reconstituted with sterile water. The two-phase regimen reflects a short plasma half-life against a factor Xa inhibitor that may still be absorbing; the label warns that re-elevation or incomplete reversal of anticoagulant activity can occur.
The target is a drug dissolved in the blood, so the decoy works entirely in the bloodstream. No cell is entered and no receptor is engaged.
╌╌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
A 41 kDa recombinant protein with the Gla domain deleted. That deletion is what stops it docking onto phospholipid membranes and assembling into the prothrombinase complex — the very feature that would have made it a clotting factor rather than a decoy.
The anticoagulant binds the decoy instead of the real enzyme
Apixaban and rivaroxaban cannot tell the difference between real factor Xa and this broken copy. They bind the copy, one molecule to one molecule, and are taken out of play.
╌╌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 active-site serine is substituted with alanine, so the protein binds the inhibitor at the catalytic site but cannot cleave prothrombin. Binding is stoichiometric and effectively irreversible over the timescale of treatment, which is why the dose is set by how much anticoagulant is present rather than by a concentration-response relationship.
Real factor Xa is freed and thrombin generation restarts
With the drug diverted, the patient’s own factor Xa is free to work again, and the cascade that builds a clot resumes within minutes.
──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
Median anti-factor-Xa activity fell 93% in apixaban patients and 94% in rivaroxaban patients in ANNEXA-4, and by 94.5% to the 1-to-2-hour nadir in ANNEXA-I against 26.9% on usual care. Median endogenous thrombin potential returned to the normal range by the end of the bolus and stayed there through 24 hours for every inhibitor studied.
Beyond mopping up the drug, the decoy also blocks one of the body’s own brakes on clotting. That is an extra shove towards a clot in someone who has just had their anticoagulant removed.
╌╌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 label states that another observed procoagulant effect of the ANDEXXA protein is its ability to bind to and inhibit tissue factor pathway inhibitor, and that inhibiting TFPI can increase tissue-factor-initiated thrombin generation. This action is independent of how much anticoagulant is being reversed, and it is the most plausible explanation for a thrombotic rate above what loss of anticoagulation alone would predict.
The haematoma stops growing — and the patient is where they were
The bleed is controlled more often than with standard treatment. Thirty days later, how disabled the patient is and whether they are alive look the same in both groups.
╌╌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
Haemostatic efficacy 67.0% against 53.1% (adjusted difference 13.4 percentage points, 95% CI 4.6 to 22.2, p=0.003), with no appreciable difference in modified Rankin scale score or 30-day death, alongside thrombotic events of 10.3% against 5.6% and ischaemic stroke of 6.5% against 1.5%. This step is the whole audit: a surrogate that moved and an outcome that did not.
No suggested links are held for this record, so nothing is hidden from this path.
What we know
The record describes 6 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 unclear◇Read 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.
Given once, in an emergency department or neurocritical care unit, to a patient with life-threatening bleeding — most often into the brain — who took a factor Xa inhibitor within the previous 15 to 18 hours.
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: “The safety and efficacy of ANDEXXA in the pediatric population have not been studied.”
US prescribing information · 2d9d90a6-63e6-46ef-96ff-dd6519ae7b6c · read 2026-08-30
On older people, the label states: “Of the 419 patients in the ANNEXA-4 study of ANDEXXA, 381 (91%) were 65 years of age or older, and 278 (66%) were older than 75 years of age.”
US prescribing information · 2d9d90a6-63e6-46ef-96ff-dd6519ae7b6c · read 2026-08-30
On people who are pregnant, the label states: “Risk Summary There are no adequate and well-controlled studies of ANDEXXA in pregnant women to inform patients of associated risks.”
US prescribing information · 2d9d90a6-63e6-46ef-96ff-dd6519ae7b6c · read 2026-08-30
On people who are breastfeeding, the label states: “Risk Summary There is no information regarding the presence of ANDEXXA in human milk, the effects on the breastfed child, or the effects on milk production.”
US prescribing information · 2d9d90a6-63e6-46ef-96ff-dd6519ae7b6c · read 2026-08-30
Where the result stopped carrying
Modified Rankin scale and 30-day mortality were unchanged in the only randomised trial, despite the primary surrogate endpoint being met
Ischaemic stroke occurred four times as often on andexanet as on usual care in patients who were already having a brain haemorrhage
Unresponsiveness to unfractionated heparin with serious thrombotic consequences was identified only after approval, from postmarketing reports, and added to the warnings section
The label states that safety has not been evaluated in patients given prothrombin complex concentrate, recombinant factor VIIa or whole blood in the preceding seven days — a common situation for the patients who receive it
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 take◇Read 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 take◇Read 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
Given by a clinician
❝ 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 bolus followed by a continuous infusion, given once in an emergency setting
✎ 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. A regulator classifies this substance in a way that restricts how it is supplied.
❝ Quoted from a source
Where this came from
Copied from a source RNAWiki stored, with the source named.
Suppression classes recorded: S6, S7.
No source is stored against this line.
What is in the pack
Supplied as 200 mg lyophilised single-dose vials, reconstituted with sterile water for injection and given as an initial bolus followed by a continuous infusion. There is no other route and no repeat course: the drug is given during the acute bleed and stopped.
✎ 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 take◇Read 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
Carries a boxed warning for arterial and venous thromboembolic events, ischaemic events including myocardial infarction and ischaemic stroke, cardiac arrest and sudden death. In the randomised trial thrombotic events occurred in 10.3% against 5.6% on usual care. Unresponsiveness to unfractionated heparin, with non-prolongation of activated clotting times and serious thrombotic events, has been reported after administration. Re-elevation or incomplete reversal of anticoagulant activity can occur. Safety has not been evaluated in patients who had a thromboembolic event or disseminated intravascular coagulation in the preceding two weeks, or who received prothrombin complex concentrate, recombinant factor VIIa or whole blood products in the preceding seven days. The commonest adverse reactions at 5% or more were urinary tract infection and pneumonia.
Nobody counted how many people took this and were fine, so this cannot be turned into a rate.
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 unclear◇Read 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 bolus followed by a continuous infusion, given once in an emergency setting
✎ 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
There is no other route and no repeat course: the drug is given during the acute bleed and stopped.
✎ 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
2 products list this as an active ingredient in the United States drug directory. 2 of them contain it and nothing else.
FDA National Drug Code directory · 42098-0006 · read 2026-08-29
They are sold as injection, powder, lyophilized, for solution and liquid, taken intravenous.
FDA National Drug Code directory · 42098-0006 · 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 · 2d9d90a6-63e6-46ef-96ff-dd6519ae7b6c · read 2026-08-29
Those labels are classed as human prescription drug.
US prescribing information · 2d9d90a6-63e6-46ef-96ff-dd6519ae7b6c · read 2026-08-29
13 marketed supplement labels list this ingredient, classed as botanical, fat/fatty acid and other combinations.
Those labels carry all other, nutrient and structure/function claims. A claim of that kind is written by the manufacturer and is not assessed by any regulator, so its presence says nothing about whether it is true.
ANDEXXA is intravenous at 3 DOSAGE FORMS AND STRENGTHS ANDEXXA is available as a white to off-white lyophilized powder in single-dose vials of 200 mg of coagulation factor Xa (recombinant), inactivated-zhzo., recorded as fda label in effect 2025-05-23 in the United States.
US prescribing information · 2d9d90a6-63e6-46ef-96ff-dd6519ae7b6c · 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 take◇Read 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 Andexanet alfa 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 unclear◇Read 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 reducing anti-factor-Xa activity improves haemostasis — the FDA states on the label that this has not been established, and made continued approval contingent on studies that show it
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 better haematoma control translates into better function or survival — the randomised trial found no appreciable difference in modified Rankin score or 30-day death
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 a 94% fall in a blood test in healthy volunteers describes what happens in an elderly patient bleeding into the brain
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 excess thrombosis is entirely the loss of anticoagulation rather than the drug’s own inhibition of tissue factor pathway inhibitor
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 unclear◇Read 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 Andexanet alfa 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 people◇Read 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 FDA wrote the caveat into the indication itself
In plain words
The label does not merely omit an outcome claim. It states in the indication that approval was based on a blood test in healthy volunteers and that an improvement in haemostasis has not been established.
What was measured
That a fall in anti-factor-Xa activity in a healthy volunteer predicts benefit in a patient bleeding into the brain — the inference the accelerated approval pathway explicitly permits and explicitly does not endorse
Effect estimate
No reviewed effect estimate exists for this record.
Limits
See the technical detail.
From the source
The ANDEXXA indication reads, in full: reversal of anticoagulation in patients treated with rivaroxaban or apixaban due to life-threatening or uncontrolled bleeding, "approved under accelerated approval based on the change from baseline in anti-FXa activity in healthy volunteers... An improvement in hemostasis has not been established. Continued approval for this indication may be contingent upon the results of studies that demonstrate an improvement in hemostasis in patients." The healthy volunteers in question were not bleeding, were not on the drug for a medical reason, and were young. Accelerated approval was granted under BLA 125586 in 2018, and the label carrying this language was still in effect on 23 May 2025.
Source
ANDEXXA FDA-approved prescribing information, section 1 Indications and Usage, label effective 23 May 2025, BLA 125586
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
Randomised at last, it did control the bleed better than usual care
In plain words
In 530 patients with a brain haemorrhage on a factor Xa inhibitor, andexanet met the primary endpoint: 67.0% achieved haemostatic control against 53.1% on usual care, most of whom got clotting factor concentrate instead.
What was measured
Composite haemostatic efficacy at 12 hours, and median reduction in anti-factor-Xa activity to nadir
Effect estimate
No reviewed effect estimate exists for this record.
Limits
See the technical detail.
From the source
ANNEXA-I randomised patients 1:1 within 15 hours of taking a factor Xa inhibitor to andexanet or usual care. The primary endpoint combined haematoma volume expansion of 35% or less at 12 hours, an increase of fewer than 7 points on the NIH Stroke Scale at 12 hours, and no rescue therapy between 3 and 12 hours. Efficacy was assessed in an interim analysis of 452 patients: 150 of 224 (67.0%) on andexanet against 121 of 228 (53.1%) on usual care, adjusted difference 13.4 percentage points (95% CI 4.6 to 22.2, p=0.003). The median reduction in anti-factor-Xa activity from baseline to the 1-to-2-hour nadir was 94.5% against 26.9% (p<0.001). Of the usual-care patients, 85.5% received prothrombin complex concentrate, so this is a comparison against active treatment, not against nothing.
Written into the record, not signed off as a reviewed claim
The same trial showed four times the ischaemic stroke rate
In plain words
Thrombotic events happened in 10.3% of the andexanet group against 5.6% on usual care. Ischaemic stroke — a clot blocking an artery in the brain, in patients already having a brain bleed — occurred in 6.5% against 1.5%.
What was measured
Thrombotic events and ischaemic stroke at 30 days in the randomised safety population
Effect estimate
No reviewed effect estimate exists for this record.
Limits
This entry records a failure.
From the source
In the 530-patient safety population of ANNEXA-I, thrombotic events occurred in 27 of 263 (10.3%) on andexanet and 15 of 267 (5.6%) on usual care, a difference of 4.6 percentage points (95% CI 0.1 to 9.2, p=0.048). Ischaemic stroke occurred in 17 patients (6.5%) against 4 (1.5%). The trial authors state the conclusion themselves: andexanet resulted in better control of haematoma expansion than usual care but was associated with thrombotic events, including ischaemic stroke. The mechanism is not only the removal of anticoagulation — andexanet also binds and inhibits tissue factor pathway inhibitor, which raises tissue-factor-initiated thrombin generation independently of the drug being reversed, an effect the label describes as a separate procoagulant action.
Written into the record, not signed off as a reviewed claim
Better haematoma control did not make the patients better
In plain words
The bleed was controlled more often, and at thirty days there was no appreciable difference in how disabled the patients were or in how many had died.
What was measured
Modified Rankin scale score and all-cause death within 30 days in the randomised population
Effect estimate
No reviewed effect estimate exists for this record.
Limits
This entry records a failure.
From the source
The ANNEXA-I report states that there were no appreciable differences between the groups in the score on the modified Rankin scale or in death within 30 days. This is the exact junction the entire reversal-agent field rests on: haematoma expansion is a strong prognostic marker, and reducing it in a randomised trial did not move the outcome it is a marker for. The trial was not powered for functional outcome, and it was stopped early once the interim efficacy analysis met its threshold, which limits what can be concluded about the null result on disability. That limitation cuts both ways — early stopping on a surrogate is precisely how a trial ends up unable to answer the question that matters.
Written into the record, not signed off as a reviewed claim
In the uncontrolled cohort, 80% achieved haemostasis and 18% died
In plain words
The single-arm study that supported approval enrolled 479 patients with major bleeding. Four in five had good or excellent haemostasis. One in ten had a clot. Of those on apixaban or rivaroxaban, 18% were dead within 45 days.
What was measured
Anti-factor-Xa activity reduction from baseline and adjudicated excellent or good haemostatic efficacy at 12 hours
Effect estimate
No reviewed effect estimate exists for this record.
Limits
See the technical detail.
From the source
ANNEXA-4 was a multicentre, prospective, phase 3b/4 single-group cohort study, mean age 78, 81% anticoagulated for atrial fibrillation, bleeding predominantly intracranial (69%) or gastrointestinal (23%). Median anti-factor-Xa activity fell from 146.9 to 10.0 ng/mL in evaluable apixaban patients (93% reduction) and from 214.6 to 10.8 ng/mL in rivaroxaban patients (94%). Excellent or good haemostasis occurred in 274 of 342 evaluable patients, 80% (95% CI 75 to 84). Thrombotic events occurred in 50 of 479 (10%). In the 419-patient apixaban-or-rivaroxaban safety population described in the label there were 75 deaths (18%), average time to death 15 days, all before day 45. There was no control group, so none of these numbers can be compared to anything.
Written into the record, not signed off as a reviewed claim
After andexanet, heparin can stop working — discovered after approval
In plain words
Patients who received andexanet and then needed heparin, for instance to go on bypass, were sometimes found not to respond to it at all, with serious clots as a result. This was added to the label from postmarketing reports, not from the trials.
What was measured
That a decoy specific to direct factor Xa inhibitors would leave other anticoagulation strategies intact — an assumption that survived the trials and failed in practice
Effect estimate
No reviewed effect estimate exists for this record.
Limits
See the technical detail.
From the source
Section 5.2 of the ANDEXXA label reports unresponsiveness to unfractionated heparin leading to non-prolongation of activated clotting times and serious thrombotic events following administration, sourced to postmarketing experience rather than to the clinical programme, with the warnings section revised as recently as March 2025. The mechanism follows from the design: andexanet sequesters the heparin-antithrombin complex as well as direct inhibitors, so the anticoagulant a cardiac surgeon depends on cannot be established. The label also warns that re-elevation or incomplete reversal of anticoagulant activity can occur, and states that safety has not been evaluated in patients who received prothrombin complex concentrate, recombinant factor VIIa or whole blood products within the preceding seven days — which is a large share of the patients the drug is used in.
Source
ANDEXXA FDA-approved prescribing information, sections 5.2 Unresponsiveness to Unfractionated Heparin and 5.3 Re-elevation or Incomplete Reversal, warnings revised March 2025
Role in the trial
Not matched to a registered study
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Written into the record, not signed off as a reviewed claim
Where else this substance is registered
FDA substance identifier (UNII)
BI009E452R
RxNorm concept
2108128
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The earliest marketing start date recorded for a listed product is 20190111.
FDA National Drug Code directory · 42098-0006 · read 2026-08-29
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A deliberately broken copy of factor Xa that circulates as a decoy and soaks up apixaban and rivaroxaban, licensed in 2018 on a blood test in healthy volunteers with the FDA stating on the label that an improvement in haemostasis had not been established — and when it was finally randomised in 530 patients with brain haemorrhage, it did control the bleed better than usual care while doubling thrombotic events, quadrupling ischaemic stroke, and leaving disability and death at 30 days unchanged.
Recorded evidence blocks (7)
Q2
On the Andexanet alfa label: indicated for what?
"ANDEXXA is indicated for patients treated with rivaroxaban or apixaban, when reversal of anticoagulation is needed due to life-threatening or uncontrolled bleeding. This indication is approved under accelerated approval based on the change from baseline in anti-FXa activity in healthy volunteers [see Clinical Studies…": indications and usage on Andexanet alfa's label. DailyMed label · 2d9d90a6-63e6-46ef-96ff-dd6519ae7b6c · 2025-05-23
Q3
11 registered trials of Andexanet alfa — at which phases?
Which 3 trials of Andexanet alfa posted no result?
Posted no result
3 of 3 completed trials
Registrations
NCT03218241, NCT03083704 and NCT05548777
Completion dates
oldest 2012-10; newest 2022-12-20
Show the evidence
Trial
NCT03218241
2012-10
NCT03083704
2017-09-28
NCT05548777
2022-12-20
Q6
At the median, Andexanet alfa's trials enrolled 153 people — anything larger?
Median enrolment
153
Largest enrolment
5480
Registered trials counted
11
Q7
What do 37 spontaneous reports say about Andexanet alfa — and not say?
These are reports people sent to a regulator. They do not show the medicine caused the reaction. Nobody counted how many people took the medicine and reported nothing. The same event can be reported more than once, and many reports are incomplete. News coverage, lawsuits and new warnings change how often people report. A count is not a rate and not a risk.
Andexanet alfa appears in spontaneous reports to regulators. Across the 9 most-reported reaction terms, 37 reaction mentions were counted: pulmonary embolism 8; acute myocardial infarction 7; cerebral infarction 6; ischaemic stroke 6. FAERS via Open Targets · CHEMBL3301583 · 2026-06-24
Show the evidence
pulmonary embolism
8
acute myocardial infarction
7
cerebral infarction
6
ischaemic stroke
6
device related thrombosis
2
embolic cerebral infarction
2
3 more recorded rows
cerebellar stroke
2
heparin resistance
2
product temperature excursion issue
2
recorded 2026-06-24 · last checked 2026-09-04
Q8
Which 9 reactions does Andexanet alfa's label not list?
ChEMBL 37 — CC BY-SA 3.0 Unported · ChEMBL ATC CC BY-SA · ClinicalTrials.gov — US Government work · Open Targets 26.06 — CC0 · mixed register set; per-register licences in docs/specs/corpus-20k-sources.md · openFDA / DailyMed — US Government work
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