This page shows what was measured, who it was measured in, and what that does not settle.
What Aflibercept does in the body
Leaking abnormal blood vessels at the back of the eye, in macular degeneration and in diabetes
The growth signals that drive these vessels work by docking into receptors on the vessel wall. Aflibercept is made from the docking parts of two of those receptors, joined together and floated free in the eye. The signals dock into it instead of into the vessels, and once caught they are held. Nothing reaches the vessel wall, so nothing tells it to grow or leak.
What happened in people
Non-inferiority to monthly ranibizumab at week 52 in 2,419 patients, with every-two-month dosing: 95.1% and 95.6% against 94.4%
✎ 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.
That aflibercept is more effective than ranibizumab in macular degeneration — every registration trial tested non-inferiority and none tested superiority
Where it acts
The vitreous cavity and the retina, reached by a needle through the white of the eye
Kind of result
The kind of result is not recorded
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 · 15C2VL427D · 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.
A limit recorded against this substance. Not signed off as a reviewed claim.
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.
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.
Non-inferiority to monthly ranibizumab in the proportion maintaining vision at week 52, 10% margin
Aflibercept 2 mg every 2 months 95.1% (VIEW 1) and 95.6% (VIEW 2) against monthly ranibizumab 94.4% in both; all regimens within 0.5 letters on mean acuity change
Repeated elsewhere
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. A non-inferiority design with a 10% margin. The trial establishes equivalence at a longer interval and cannot establish superiority, which it is frequently quoted as showing.
How far it carries. This study is recorded from the curated record, not from the registry match.
Form and route. Intravitreal injection of 2 mg in 50 microlitres, or 8 mg in the high-dose formulation
Interval reported. Not recorded in this summary
Written into the record, not signed off as a reviewed claim.
+13.3 aflibercept, +9.7 bevacizumab, +11.2 ranibizumab; P<0.001 and P=0.03 respectively, with P<0.001 for interaction with baseline acuity
Repeated elsewhere
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. The overall superiority is entirely attributable to eyes with baseline acuity below 69 letters. In the 51% of patients above that threshold all three drugs were indistinguishable, P>0.50 for every pairwise comparison. The paper states the overall difference was not clinically meaningful.
How far it carries. This study is recorded from the curated record, not from the registry match.
Form and route. Intravitreal injection of 2 mg in 50 microlitres, or 8 mg in the high-dose formulation
Interval reported. Not recorded in this summary
Written into the record, not signed off as a reviewed claim.
+6.7 (8q12) and +6.2 (8q16) against +7.6 (2q8) letters; least squares mean differences -0.97 (95% CI -2.87 to 0.92) and -1.14 (-2.97 to 0.69) against a 4-letter margin
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. Both high-dose point estimates fall below the standard-dose comparator. Dosing intervals in the 8 mg groups could be shortened from week 16 on prespecified disease-activity criteria, so the arms were not held to fixed schedules. Funded by Bayer AG and Regeneron, with employees of both among the authors.
How far it carries. This study is recorded from the curated record, not from the registry match.
Form and route. Intravitreal injection of 2 mg in 50 microlitres, or 8 mg in the high-dose formulation
Interval reported. 95% CI -2
Written into the record, not signed off as a reviewed claim.
Hazard ratio 0.817 (95.34% CI 0.713 to 0.937), P = .0032; median survival 13.50 against 12.06 months
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. The absolute survival difference is 1.44 months. Toxicity included anti-VEGF class effects plus an increased incidence of some chemotherapy-related toxicities. This is a different route, dose and approval from the ophthalmic product and is included because it is the same protein and the source of the pricing episode on this page.
How far it carries. This study is recorded from the curated record, not from the registry match.
Form and route. Intravitreal injection of 2 mg in 50 microlitres, or 8 mg in the high-dose formulation
Interval reported. Not recorded in this summary
Written into the record, not signed off as a reviewed claim.
RNAWiki holds 4 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
Aflibercept
What a person takes: Intravitreal injection of 2 mg in 50 microlitres, or 8 mg in the high-dose formulation.
The measurement behind this step
A needle through the pars plana into the vitreous cavity, under topical anaesthetic and antisepsis. In the pivotal programme, three initial monthly doses were followed by injection every two months. The 8 mg formulation extends the interval further, to every 12 or 16 weeks, with shortening permitted if disease activity criteria are met. The same protein is given intravenously under a separate approval and name for metastatic colorectal cancer.
Getting in
A needle into the jelly of the eye
The drug is injected directly into the vitreous through the white of the eye. There is no way to get a protein this size to the back of the eye from a tablet or a drop.
──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
Intravitreal injection of 2 mg in 50 microlitres through the pars plana. The 50 microlitre volume constraint drives the formulation: the protein must be concentrated enough to deliver the dose in a volume the eye can absorb without a sustained pressure rise. Ocular adverse events in the study eye occurred in 38% to 39% of patients across all groups in PULSAR.
This is not an antibody. It is the docking parts of two receptors, taken from where they sit on the vessel wall, joined together and set loose in the eye.
──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
Aflibercept fuses domain 2 of VEGFR-1 and domain 3 of VEGFR-2 to the Fc portion of human IgG1, giving a homodimeric glycoprotein of approximately 115 kDa. Each of the two receptor domains was chosen for its affinity contribution, rather than either receptor being copied whole. The Fc drives dimerisation and gives a two-armed trap.
The signalling proteins fit into the decoy the way they would fit into a real receptor, and once in they stay. Three different signals are caught, where the competing drugs catch one.
╌╌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
Aflibercept binds VEGF-A, VEGF-B and placental growth factor, preventing their engagement with VEGFR-1 and VEGFR-2 on endothelial cells. The high-affinity, slowly dissociating interaction is what the word "trap" refers to and is the pharmacological basis for the extended dosing interval, although no trial has isolated affinity from molecular size as the cause of that duration.
With the signals captured, the receptors on the abnormal vessels never fire. Growth stops and the leak dries up.
╌╌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
Blocking VEGFR-1 and VEGFR-2 engagement suppresses the endothelial proliferation, migration and permeability signalling that drives choroidal neovascularisation and macular oedema. Anatomic improvement in the VIEW integrated analysis was similar across all aflibercept regimens and monthly ranibizumab.
Nineteen in twenty patients kept their vision at one year on injections every two months, the same as the comparator drug given every month.
──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
At week 52, 95.1% and 95.6% of patients on aflibercept 2 mg every two months maintained vision in VIEW 1 and VIEW 2, against 94.4% on monthly ranibizumab in both, meeting non-inferiority at a 10% margin. All aflibercept regimens were within 0.5 letters of ranibizumab on mean acuity change in the prespecified integrated analysis.
And where vision is already poor, the drug choice starts to matter
In diabetic swelling of the retina, three drugs that differ forty-fold in price gave the same result in patients who could still see reasonably well. In those who could not, aflibercept was clearly better.
╌╌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
In Protocol T, at baseline letter scores of 78 to 69 the one-year gains were 8.0 with aflibercept, 7.5 with bevacizumab and 8.3 with ranibizumab, with P>0.50 for every pairwise comparison. Below 69 letters they were 18.9, 11.8 and 14.2, with P<0.001 for aflibercept against bevacizumab. The interaction with baseline acuity was significant at P<0.001.
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.
Adults with wet macular degeneration, diabetic macular oedema, diabetic retinopathy or retinal vein occlusion, and — at a different dose and under a separate part of the label — premature infants with retinopathy of prematurity.
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 effectiveness in pediatric patients have not been established.”
US prescribing information · f6725df6-50ee-4b0a-b900-d02ba634395d · read 2026-08-30
On older people, the label states: “Of the 611 patients with mCRC, patients treated with ZALTRAP/FOLFIRI, 205 (34%) were 65 years or older, and 33 (5%) were 75 years or older.”
US prescribing information · f6725df6-50ee-4b0a-b900-d02ba634395d · read 2026-08-30
On people who are pregnant, the label states: “Risk Summary Based on findings from animal reproduction studies and its mechanism of action [see Clinical Pharmacology (12.1) ] , ZALTRAP can cause fetal harm when administered to pregnant women.”
US prescribing information · f6725df6-50ee-4b0a-b900-d02ba634395d · read 2026-08-30
On people who are breastfeeding, the label states: “Risk Summary There are no data on the presence of ziv-aflibercept in human milk, or the effects of ziv-aflibercept on the breastfed infant or on milk production.”
US prescribing information · f6725df6-50ee-4b0a-b900-d02ba634395d · read 2026-08-30
On people with reduced liver function, the label states: “No dosage modification is recommended for patients with mild (total bilirubin >1 to 1.5 times upper limit normal [ULN] and any aspartate transaminase [AST]) and moderate (total bilirubin >1.5 to 3 times ULN and any AST) hepatic impairment [see Clinical Pharmacology (12.3) ] .”
US prescribing information · f6725df6-50ee-4b0a-b900-d02ba634395d · read 2026-08-30
On people with reduced kidney function, the label states: “No dosage modification is recommended for patients with renal impairment [see Clinical Pharmacology (12.3) ] .”
US prescribing information · f6725df6-50ee-4b0a-b900-d02ba634395d · read 2026-08-30
Where the result stopped carrying
The Protocol T advantage disappears in the 51% of diabetic macular oedema patients whose starting vision was better than about 20/50, where three drugs differing forty-fold in price were indistinguishable
PULSAR’s high-dose arms recorded -0.97 and -1.14 letters relative to the standard dose, and were allowed to shorten their intervals mid-trial
The intravenous formulation of the same protein extended median survival in colorectal cancer by 1.44 months, and its launch price prompted a cancer centre to refuse to stock it in public
No biosimilar competition existed for the first thirteen years after approval
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.
There was nothing to correct
Where a level is already normal, topping it up may change nothing.
On this record: The preferred agent in diabetic macular oedema with worse baseline acuity, on the strength of an independently funded head-to-head trial
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 (10)
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.
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
Prescription only
❝ 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
Intravitreal injection of 2 mg in 50 microlitres, or 8 mg in the high-dose formulation
✎ 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: S1, S3, S4.
No source is stored against this line.
What is in the pack
A needle through the pars plana into the vitreous cavity, under topical anaesthetic and antisepsis. In the pivotal programme, three initial monthly doses were followed by injection every two months. The 8 mg formulation extends the interval further, to every 12 or 16 weeks, with shortening permitted if disease activity criteria are met. The same protein is given intravenously under a separate approval and name for metastatic colorectal cancer.
✎ 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
Endophthalmitis, retinal detachment, intraocular inflammation, raised intraocular pressure and traumatic cataract are the recognised risks of intravitreal injection, and the risk is per injection in a treatment that continues indefinitely. In PULSAR, ocular adverse events in the study eye occurred in 38% to 39% of patients across all three dose groups. Systemic arterial thromboembolic events are a theoretical class concern; Protocol T found no significant differences among aflibercept, bevacizumab and ranibizumab in serious adverse events, hospitalisation, death or major cardiovascular events. The intravenous oncology formulation carries a different and far heavier toxicity profile, including anti-VEGF class effects and increased chemotherapy-related toxicity, and its safety information does not transfer to the ophthalmic product.
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
Intravitreal injection of 2 mg in 50 microlitres, or 8 mg in the high-dose formulation
✎ 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
In the pivotal programme, three initial monthly doses were followed by injection every two months. The 8 mg formulation extends the interval further, to every 12 or 16 weeks, with shortening permitted if disease activity criteria are met. The same protein is given intravenously under a separate approval and name for metastatic colorectal cancer.
✎ 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
16 products list this as an active ingredient in the United States drug directory. 16 of them contain it and nothing else.
FDA National Drug Code directory · 83277-004 · read 2026-08-29
They are sold as injection, solution, liquid, solution and solution, concentrate, taken intravenous and intravitreal.
FDA National Drug Code directory · 83277-004 · read 2026-08-29
The regulator's established pharmacologic class for it is vascular endothelial growth factor inhibitor [epc] and vascular endothelial growth factor inhibitors [moa].
FDA National Drug Code directory · 83277-004 · read 2026-08-29
5 published labels name it as an active ingredient. 5 of them describe this substance alone, which is where its own label text on this page comes from.
US prescribing information · f96cfd69-da34-41ee-90a9-610a4655cd1c · read 2026-08-29
Those labels are classed as human prescription drug.
US prescribing information · f96cfd69-da34-41ee-90a9-610a4655cd1c · read 2026-08-29
ZALTRAP is intravenous at 3 DOSAGE FORMS AND STRENGTHS ZALTRAP is a clear, colorless to pale-yellow solution available as: Injection: 100 mg/4 mL (25 mg/mL) solution in a single-dose vial Injection: 200 mg/8 mL (25 mg/mL) solution in a single-do…, recorded as fda label in effect 2025-10-06 in the United States.
US prescribing information · f6725df6-50ee-4b0a-b900-d02ba634395d · 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 Aflibercept 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 aflibercept is more effective than ranibizumab in macular degeneration — every registration trial tested non-inferiority and none tested superiority
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 binding VEGF-B and placental growth factor produces a better visual outcome, which no head-to-head trial has demonstrated
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 extended dosing interval follows from the broader target set rather than from affinity and molecular size, which nobody has separated
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 8 mg formulation is an improvement, when both of its point estimates in PULSAR fall below the standard dose
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.
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 Aflibercept 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.
VIEW 1 and VIEW 2: matched monthly ranibizumab at half the injections
In plain words
Two identical trials in 2,419 patients compared aflibercept, given monthly or every two months, against ranibizumab given monthly. Every aflibercept schedule matched the monthly comparator, including the two-monthly one.
What was measured
Proportion maintaining vision at week 52, aflibercept regimens against monthly ranibizumab, 10% non-inferiority margin
Effect estimate
No reviewed effect estimate exists for this record.
Limits
See the technical detail.
From the source
VIEW 1 and VIEW 2 were double-masked, multicentre, parallel-group, active-controlled randomised trials in 2,419 patients with active subfoveal choroidal neovascularisation secondary to age-related macular degeneration, or juxtafoveal lesions with leakage affecting the fovea. Patients were randomised to intravitreal aflibercept 0.5 mg monthly, 2 mg monthly, 2 mg every two months after three initial monthly doses, or ranibizumab 0.5 mg monthly. The primary endpoint was non-inferiority with a 10% margin on the proportion maintaining vision at week 52, defined as losing fewer than 15 ETDRS letters. All aflibercept groups were non-inferior and clinically equivalent: 95.1%, 95.9% and 95.1% in VIEW 1 and 95.6%, 96.3% and 95.6% in VIEW 2, against monthly ranibizumab at 94.4% in both. In a prespecified integrated analysis, all aflibercept regimens were within 0.5 letters of ranibizumab on mean acuity change, with similar anatomic improvement and similar ocular and systemic adverse events.
Written into the record, not signed off as a reviewed claim
Protocol T: the advantage exists, and only where vision is already poor
In plain words
A publicly funded trial compared all three drugs in diabetic macular oedema. Aflibercept came out ahead overall. But split the patients by how well they saw at the start and the advantage vanishes entirely in the better-seeing half.
What was measured
Mean change in visual acuity at 1 year, stratified by baseline visual acuity, three drugs head to head
Effect estimate
No reviewed effect estimate exists for this record.
Limits
See the technical detail.
From the source
The Diabetic Retinopathy Clinical Research Network randomised 660 adults with centre-involved diabetic macular oedema at 89 sites to aflibercept 2.0 mg, bevacizumab 1.25 mg or ranibizumab 0.3 mg, given as often as every four weeks by protocol algorithm. From baseline to one year, mean visual-acuity letter score improved by 13.3 with aflibercept, 9.7 with bevacizumab and 11.2 with ranibizumab. Aflibercept was superior to both (P<0.001 against bevacizumab, P=0.03 against ranibizumab), but the paper states the improvement was not clinically meaningful because the difference was driven by eyes with worse baseline acuity (P<0.001 for interaction). Where the initial letter score was 78 to 69, roughly 20/32 to 20/40 and 51% of participants, mean improvement was 8.0, 7.5 and 8.3 with P>0.50 for every pairwise comparison. Where it was below 69, roughly 20/50 or worse, it was 18.9, 11.8 and 14.2, with P<0.001 for aflibercept against bevacizumab, P=0.003 against ranibizumab and P=0.21 for ranibizumab against bevacizumab. There were no significant differences in serious adverse events, hospitalisation, death or major cardiovascular events.
Written into the record, not signed off as a reviewed claim
Three targets instead of one, and no trial has shown the extra two matter
In plain words
Aflibercept catches two growth signals its competitors miss, and this is the main thing said about it. No trial has demonstrated that catching them produces better vision.
What was measured
That binding VEGF-B and placental growth factor in addition to VEGF-A produces a clinically better drug — a mechanistic distinction with no demonstrated visual consequence in any head-to-head trial
Effect estimate
No reviewed effect estimate exists for this record.
Limits
See the technical detail.
From the source
Aflibercept binds VEGF-A, VEGF-B and placental growth factor, where ranibizumab and bevacizumab bind VEGF-A alone. The broader target set is the pharmacological rationale for the molecule and is stated on the label. What no trial has established is a visual consequence. In VIEW 1 and VIEW 2 all aflibercept regimens fell within 0.5 letters of monthly ranibizumab — the design was non-inferiority, and the result was equivalence rather than superiority. In Protocol T the superiority over ranibizumab was P=0.03 overall and absent in the 51% of patients with better baseline acuity. The one clinical property the broader binding plausibly supports is duration, and duration is what the two-monthly dosing schedule in VIEW actually demonstrated. Attributing the interval to placental growth factor blockade rather than to affinity and molecular size remains an inference nobody has tested by removing one variable.
Written into the record, not signed off as a reviewed claim
The high-dose version’s point estimates run against it
In plain words
Four times the dose, given at longer intervals, was declared non-inferior. Both high-dose arms actually recorded slightly less vision gain than the standard dose, and the trial was funded by the two companies that sell it.
What was measured
Change from baseline in best corrected visual acuity at week 48, 8 mg extended intervals against 2 mg every 8 weeks
Effect estimate
No reviewed effect estimate exists for this record.
Limits
This entry records a failure.
From the source
PULSAR randomised 1,011 patients with neovascular age-related macular degeneration 1:1:1 to aflibercept 8 mg every 12 weeks, 8 mg every 16 weeks, or 2 mg every 8 weeks, after three initial monthly doses in all groups, with dosing interval shortening permitted in the 8 mg groups from week 16 if prespecified disease-activity criteria were met. Mean best corrected visual acuity change from baseline at week 48 was +6.7 letters (SD 12.6) for 8q12 and +6.2 (11.7) for 8q16, against +7.6 (12.2) for 2q8. Least squares mean differences against 2q8 were -0.97 letters (95% CI -2.87 to 0.92) and -1.14 (-2.97 to 0.69), against a 4-letter non-inferiority margin. Ocular adverse events in the study eye were similar across groups at 39%, 38% and 39%. The trial was funded by Bayer AG and Regeneron Pharmaceuticals, and the author list includes employees of both. Non-inferiority was met. Both point estimates favour the older, cheaper, more frequent regimen, and the permitted interval shortening means the 8 mg arms were not held to a fixed schedule.
Written into the record, not signed off as a reviewed claim
The same protein in oncology was the first drug a hospital refused on price
In plain words
Given into a vein for bowel cancer, this protein extends median survival by about six weeks. When it launched at roughly twice the price of an equivalent drug, Memorial Sloan Kettering announced in a newspaper that it would not stock it. The price was halved.
What was measured
That a statistically significant survival benefit justifies any price — a premise a cancer centre challenged in public over this molecule, and the manufacturer conceded within weeks
Effect estimate
No reviewed effect estimate exists for this record.
Limits
See the technical detail.
From the source
The VELOUR trial randomised 1,226 patients with metastatic colorectal cancer previously treated with oxaliplatin to aflibercept 4 mg/kg intravenously or placebo, every two weeks with FOLFIRI. Overall survival improved with a hazard ratio of 0.817 (95.34% CI 0.713 to 0.937, P=.0032) and median survival of 13.50 against 12.06 months — a difference of 1.44 months. Progression-free survival improved from 4.67 to 6.90 months (HR 0.758, P<.0001) and response rate from 11.1% to 19.8% (P=.0001). Toxicity included the characteristic anti-VEGF effects plus increased incidence of some chemotherapy-related toxicities. The drug was approved in 2012 as ziv-aflibercept under a separate application, at a launch price that led Memorial Sloan Kettering Cancer Center to state publicly that it would not use it, on the grounds that it offered no advantage over a much cheaper alternative. Sanofi subsequently halved the effective price through discounting. The episode is cited as the point at which cost entered formulary decisions as an explicit clinical argument rather than an administrative one.
Written into the record, not signed off as a reviewed claim
Every pivotal trial asked whether it could tie, not whether it could win
In plain words
VIEW, PULSAR and the whole registration programme were non-inferiority trials. A non-inferiority result means the new drug is not meaningfully worse. It does not mean it is better, and it is routinely reported as though it did.
What was measured
That aflibercept is more effective than ranibizumab — a claim no registration trial was designed to test and none has demonstrated
Effect estimate
No reviewed effect estimate exists for this record.
Limits
See the technical detail.
From the source
VIEW 1 and VIEW 2 tested non-inferiority against monthly ranibizumab with a 10% margin on the proportion maintaining vision, and the integrated analysis reported all aflibercept regimens within 0.5 letters of the comparator. PULSAR tested non-inferiority of 8 mg extended intervals against 2 mg every 8 weeks with a 4-letter margin, and both 8 mg point estimates fell below the comparator. The one trial in this dossier that tested superiority head to head was Protocol T, which is independently funded, and its superiority finding was confined to eyes with worse baseline acuity and described by its own authors as not clinically meaningful overall. The commercial proposition for aflibercept — equivalent vision with fewer injections — is genuinely supported. The frequent restatement of that as aflibercept being the more effective drug is not what any of these trials measured.
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What is not here
7 questions this page could not answer
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What was measured, goal by goal — found nothing in the sources checked.
How close this is to real life — found nothing in the sources checked.
Felt, measured, or meaningful — found nothing in the sources checked.
How long anything takes — found nothing in the sources checked.
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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.
A soluble decoy built from two different VEGF receptors fused to an antibody tail, which binds VEGF-A, VEGF-B and placental growth factor and, given every two months after three loading doses, matched monthly ranibizumab in 2,419 patients — 95.1% and 95.6% maintaining vision against 94.4% — and beat both bevacizumab and ranibizumab in diabetic macular oedema only in the half of patients whose vision was already worse.
Recorded evidence blocks (9)
Q2
On the Aflibercept label: indicated for what?
"ZALTRAP, in combination with fluorouracil, leucovorin, irinotecan-(FOLFIRI), is indicated for the treatment of patients with metastatic colorectal cancer (mCRC) that is resistant to or has progressed following an oxaliplatin-containing regimen. ZALTRAP, a vascular endothelial growth factor inhibitor, in combination…": indications and usage on Aflibercept's label. DailyMed label · f6725df6-50ee-4b0a-b900-d02ba634395d · 2025-10-06
Q3
443 registered trials of Aflibercept — at which phases?
Registered studies posting no result
282 of 443
443 registered studies of Aflibercept: 140 phase2, 108 phase3, 84 phase4, 64 na or unstated, 55 phase1, 20 na, 2 early phase1. CLINICALTRIALS_SNAPSHOT · 2026-09-01
terminated; "Early termination for discouraging results"
NCT00574275
terminated; "Data Monitoring Committee concluded after a planned interim analysis that aflibercept added to gemcitabine would be unable to demonstrate improved survival"
NCT00601991
withdrawn; "Another study was opened."
NCT01669720
terminated; "Lack of efficacy and enrollment"
NCT01746875
terminated; "treatment effects not as desired"
14 further recorded trials
NCT01868360
terminated; "Lack of enrollment"
NCT01941173
withdrawn; "Lack of accrual"
NCT01955629
terminated; "The study enrollment was prematurely halted due to safety reasons."
NCT01965041
withdrawn; "No patients enrolled."
NCT02002377
terminated; "Inadequate enrollment due to investigational product becoming newly available on the Canadian market soon after study start"
NCT02045030
terminated; "Drug (Aflibercept) no longuer available for the study"
NCT02079220
withdrawn; "Funding for the study was withdrawn, no participants were ever recruited."
NCT02192541
terminated; "Drug supplier suspended further clinical development of Ganetespib"
NCT02235324
withdrawn; "Lack of funding"
NCT02348359
terminated; "Interim analysis found study had achieved primary objective"
NCT02418754
terminated; "No additional efficacy seen with REGN2176-3 over aflibercept alone"
NCT02797704
terminated; "the treatment was found to be inefficient for all recruited patients"
NCT02980874
terminated; "Primary, 8-week efficacy endpoint not achieved. No additional benefit for subjects receiving a corticosteroid together with an intravitreal anti-VEGF agent."
NCT03059277
withdrawn; "Site investigator decided to not move forward with study."
recorded 2026-09-01 · last checked 2026-09-04
Q5
Human studies of Aflibercept used Intravitreal Aflibercept Injection 2mg — over how long?
studies of Aflibercept used the recorded amount. ClinicalTrials.gov · 2026-09-01
20 recorded entries; human; intravitreal, injection; also "Intravitreal Aflibercept Injection 2mg", "0.5 mg Lucentis or 1.25 mg Avastin or 2 mg Eylea", "aflibercept 2.0 mg"
intravitreal; Aflibercept intravitreal injection of 0,5 mg ( 0.05mL
humanNCT02130024
Aflibercept 2.0 mg
humanNCT02257632
Aflibercept 2 mg
humanNCT02309281
aflibercept 2mg
humanNCT02309281
Eylea 2mg
humanNCT02645734
ziv-aflibercept 1.25 mg
humanNCT02645734
ziv-aflibercept 2.5mg
humanNCT03423823
Ziv-Aflibercept 25 MG/ML [Zaltrap]
humanNCT03577899
2.0 mg Aflibercept Intravitreal Injection
humanNCT04527107
THR-149 0.13mg + aflibercept 2mg
humanNCT04527107
aflibercept 2mg + THR-149 0.13mg
recorded 2026-09-01 · last checked 2026-09-04
Q6
Aflibercept's half-life is 6 days — which schedules were studied?
6 days, the half-life Aflibercept's label states: "Elimination Following a dose of 4 mg per kg every two weeks administered intravenously, the elimination half-life of free ziv-aflibercept was approximately 6 days (range 4–7 days)." DailyMed label · f6725df6-50ee-4b0a-b900-d02ba634395d · 2025-10-06
Show the evidence
half lifepharmacokinetics
6 days; Elimination Following a dose of 4 mg per kg every two weeks administered intravenously, the elimination half-life of free ziv-aflibercept was approximately 6 days (range 4–7 days).
recorded 2025-10-06 · last checked 2026-09-04
Q7
Which 126 trials of Aflibercept posted no result?
Posted no result
126 of 126 completed trials
Registrations
NCT00383370, NCT00320775, NCT00876044, NCT00479076, NCT00644124 and NCT01148615, and 120 more
Completion dates
oldest 2008-07; newest 2024-08-20
Show the evidence
Trial
NCT00383370
2008-07
NCT00320775
2008-08
NCT00876044
2010-11
NCT00479076
2011-01
NCT00644124
2011-10
NCT01148615
2011-12
14 further recorded trials
NCT00921661
2012-06
NCT00545246
2012-07
NCT00650923
2013-12
NCT02309281
2014-07
NCT01724554
2014-10
NCT01688960
2014-11
NCT01824225
2015-03
NCT01971190
2015-05
NCT01896284
2015-06
NCT02291887
2015-07-01
NCT01722656
2015-09
NCT01997164
2015-10
NCT02641457
2015-10
NCT02646670
2015-11
Q8
At the median, Aflibercept's trials enrolled 64 people — anything larger?
Median enrolment
64
Largest enrolment
550000
Registered trials counted
440
Q9
What do 3728 spontaneous reports say about Aflibercept — 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.
Aflibercept appears in spontaneous reports to regulators. Across the 10 most-reported reaction terms, 3728 reaction mentions were counted: blindness 556; endophthalmitis 535; visual impairment 516; visual acuity reduced 414. FAERS via Open Targets · CHEMBL1742982 · 2026-06-24
Show the evidence
blindness
556
endophthalmitis
535
visual impairment
516
visual acuity reduced
414
blindness transient
361
hypertension
309
4 more recorded rows
vision blurred
281
blindness unilateral
257
eye inflammation
257
intraocular pressure increased
242
recorded 2026-06-24 · last checked 2026-09-04
Q10
Which 10 reactions does Aflibercept'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
✗ 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: 6 source rows
✓ no critical contamination: no quarantine open
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✓ no raw internal fields: enforced by the copy-contract test over the rendered page
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