This page shows what was measured, who it was measured in, and what that does not settle.
What Etranacogene dezaparvovec does in the body
One infusion, and for most patients the weekly injections stop.
Your liver is supposed to make a clotting protein and does not. A harmless virus shell carries a working copy of the gene into liver cells, where it stays as a separate loop of DNA and starts producing the protein. The copy delivered is not the ordinary version — it is a naturally occurring variant found in an Italian family, about eight times more active than normal, so even modest production gives a useful clotting level.
Why people take it. Haemophilia B in adults
What happened in people
Annualised bleeding rate 4.19 during prophylaxis lead-in versus 1.51 during months 7 to 18 after treatment, rate ratio 0.36 (P<0.001)
✎ 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.
HOPE-B: Trial of AMT-061 in Severe or Moderately Severe Hemophilia B Patients (NCT03569891) · a recorded source, not a stored snapshot
The limit that matters most
That the effect is lifelong — five years is the measured horizon and hepatocytes do turn over
Where it acts
Liver hepatocyte nucleus
Kind of result
The kind of result is not recorded
Supervision
Professional supervision is normally required. It is a prescription or clinician-administered medicine where it is approved.
What the registries record it as
The substance registry classes this as structurallydiverse.
FDA substance registry · Z5XCD5Q9RL · read 2026-08-29
The material is recorded as coming from recombinant virus.
FDA substance registry · Z5XCD5Q9RL · read 2026-08-29
Where each sentence above came from
A person wrote this explanation into the record, with the studies named in the path below.
The recorded use, written for a reader without medical training. Not signed off.
A limit recorded against this substance. Not signed off as a reviewed claim.
The four opening statements run to 114 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.
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.
Annualised bleeding rate during months 7 to 18 after treatment compared with the prophylaxis lead-in period, tested for non-inferiority against a margin of 1.8
✓ The study showed what it set out to show
Who was studied
HOPE-B (NCT03569891)
How many people
54
Study design
Phase 3, open label, single group with prospective prophylaxis lead-in
Compared against
Not recorded for this study
Kind of result
A number that stands in for health
What was found
P < 0.001; rate ratio 0.36 (95% Wald CI 0.20 to 0.64)
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. No treatment-related serious adverse events in the primary analysis. One case of hepatocellular carcinoma in a participant with extensive independent risk factors triggered an FDA clinical hold in December 2020; independent integration analysis concluded the tumour was unrelated to treatment.
How far it carries. This study is recorded from the curated record, not from the registry match.
Form and route. Recombinant AAV5 vector, single intravenous infusion
Interval reported. Not recorded in this summary
Written into the record, not signed off as a reviewed claim.
HOPE-B: Trial of AMT-061 in Severe or Moderately Severe Hemophilia B Patients (NCT03569891) · a recorded source, not a stored snapshot
FDA HEMGENIX product page and package insert (https://www.fda.gov/vaccines-blood-biologics/vaccines/hemgenix) · a recorded source, not a stored snapshot
Adjusted annualised bleeding rate months 7 to 60 versus lead-in, plus factor IX expression and safety
✓ The study showed what it set out to show
Who was studied
HOPE-B five-year final analysis (NCT03569891)
How many people
54
Study design
Phase 3, prespecified five-year analysis
Compared against
Not recorded for this study
Kind of result
A number that stands in for health
What was found
63% reduction in annualised bleeding rate (95% CI 24 to 82)
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. Adverse events possibly related to treatment were rare after month 6. Long-term hepatic surveillance remains a class requirement rather than a resolved question.
How far it carries. This study is recorded from the curated record, not from the registry match.
Form and route. Recombinant AAV5 vector, single intravenous infusion
Interval reported. 95% CI 24 to 82)
Written into the record, not signed off as a reviewed claim.
HOPE-B: Trial of AMT-061 in Severe or Moderately Severe Hemophilia B Patients (NCT03569891) · a recorded source, not a stored snapshot
FDA HEMGENIX product page and package insert (https://www.fda.gov/vaccines-blood-biologics/vaccines/hemgenix) · a recorded source, not a stored snapshot
What we know
RNAWiki holds 2 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
Etranacogene dezaparvovec
What a person takes: Recombinant AAV5 vector, single intravenous infusion.
The measurement behind this step
One intravenous infusion of 2 x 10^13 genome copies per kg body weight, given in a single session with no conditioning, no surgery and no prophylactic immunosuppression. Corticosteroid is reserved for reactive management of transaminase elevation.
Getting in
A single intravenous infusion
One infusion into a vein. No chemotherapy, no surgery, no cells taken out of the body.
╌╌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 single dose of 2 x 10^13 genome copies per kg of AAV5 vector is infused intravenously. Corticosteroid is not given prophylactically; it is started reactively if transaminases rise.
HOPE-B: Trial of AMT-061 in Severe or Moderately Severe Hemophilia B Patients (NCT03569891) · a recorded source, not a stored snapshot
Reaching the cell
The AAV5 shell is taken up by liver cells
The blood carries the whole dose through the liver, where the shell is absorbed by the cells that make clotting proteins.
╌╌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
AAV5 has strong natural hepatotropism after systemic administration. Uptake is receptor-mediated and the vast majority of the dose is cleared by the liver on first pass, which is why a liver-expressed protein is the natural target for systemic AAV.
HOPE-B: Trial of AMT-061 in Severe or Moderately Severe Hemophilia B Patients (NCT03569891) · a recorded source, not a stored snapshot
What it acts on
A liver-only promoter keeps expression where it belongs
The delivered gene comes with a switch that only liver cells can read, so it does not start producing clotting factor anywhere else.
╌╌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 codon-optimised factor IX Padua cassette is driven by the liver-specific LP1 promoter and persists as a non-integrating nuclear episome. Restricting expression to hepatocytes limits both off-target production and the immune presentation of the transgene product elsewhere.
HOPE-B: Trial of AMT-061 in Severe or Moderately Severe Hemophilia B Patients (NCT03569891) · a recorded source, not a stored snapshot
The change it makes
The gene delivered is a hyperactive natural variant
The copy inserted is not the standard one. It is a variant found in an Italian family whose members clot about eight times more efficiently per molecule, so a little protein goes a long way.
╌╌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
Factor IX Padua carries an arginine-to-leucine substitution at position 338, first identified in a family with unexplained thrombophilia, conferring roughly eight-fold higher specific activity. This is the single design decision that made haemophilia B gene therapy clinically useful: it converts a modest, achievable expression level into a therapeutic clotting activity.
HOPE-B: Trial of AMT-061 in Severe or Moderately Severe Hemophilia B Patients (NCT03569891) · a recorded source, not a stored snapshot
What that does for a person
Bleeding falls, and stays fallen for five years
Bleeds dropped by about two thirds, weekly infusions largely stopped, and five years on the clotting factor level was still around a third of normal.
──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
Annualised bleeding rate 4.19 to 1.51 in the primary analysis (rate ratio 0.36); at five years, adjusted annualised bleeding rate 4.16 to 1.52, mean factor IX activity 36.1 ± 15.7 IU/dL, and a 96% reduction in exogenous factor IX consumption. Post-mitotic hepatocyte turnover in adults is slow enough that episomal loss did not materially erode expression over that horizon.
HOPE-B: Trial of AMT-061 in Severe or Moderately Severe Hemophilia B Patients (NCT03569891) · a recorded source, not a stored snapshot
No suggested links are held for this record, so nothing is hidden from this path.
What we know
The record describes 5 steps from taking it to an effect in a person.
How we know it
Each step names the study behind it in the technical detail beside it.
What this does not prove
A change inside the body is a reason to look. It is not a result in a person.
Why it matters
A reader can see exactly where the chain stops being measured in people.
What we still do not know
No reviewed claim binds any of these steps to a named population.
What is missing or 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 on factor IX prophylaxis, or with a history of life-threatening or repeated serious bleeding. Unusually for this field, patients were enrolled regardless of pre-existing antibodies to the AAV5 capsid.
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 HEMGENIX in pediatric patients have not been established.”
US prescribing information · 35b2db65-4c6c-4173-ab56-b2bca69193bd · read 2026-08-30
On older people, the label states: “The clinical studies included a total of 6 geriatric patients with Hemophilia B, aged 68 to 75 years at time of enrollment.”
US prescribing information · 35b2db65-4c6c-4173-ab56-b2bca69193bd · read 2026-08-30
On people who are pregnant, the label states: “Risk Summary HEMGENIX is not intended for administration in women.”
US prescribing information · 35b2db65-4c6c-4173-ab56-b2bca69193bd · read 2026-08-30
On people with reduced liver function, the label states: “Limited clinical data in patients with liver impairment indicate numerically lower FIX activity as compared to patients without hepatic impairment [see Clinical Pharmacology (12.3) ] .”
US prescribing information · 35b2db65-4c6c-4173-ab56-b2bca69193bd · read 2026-08-30
On people with reduced kidney function, the label states: “Limited clinical data are available in patients with mild and moderate renal impairment [see Clinical Pharmacology (12.3) ] .”
US prescribing information · 35b2db65-4c6c-4173-ab56-b2bca69193bd · read 2026-08-30
Where the result stopped carrying
An FDA clinical hold in December 2020 after a hepatocellular carcinoma case, resolved only after independent vector integration and whole genome analysis
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
Recombinant AAV5 vector, single intravenous infusion
✎ Source-linked record
Where this came from
A person wrote this into the record with the study named beside it. No reviewer has signed it off.
The form and route recorded on this substance.
No source is stored against this line.
Who oversees it
Professional supervision is normally required. It is a prescription or clinician-administered medicine where it is approved.
❝ Quoted from a source
Where this came from
Copied from a source RNAWiki stored, with the source named.
The identity record classes it as CRISPR / Gene Therapy.
No source is stored against this line.
What is in the pack
One intravenous infusion of 2 x 10^13 genome copies per kg body weight, given in a single session with no conditioning, no surgery and no prophylactic immunosuppression. Corticosteroid is reserved for reactive management of transaminase elevation.
✎ 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
No boxed warning. The principal labelled concerns are infusion reactions, hepatotoxicity with transaminase elevation requiring monitoring and possible corticosteroid treatment, and the theoretical risk of hepatocellular carcinoma warranting long-term liver surveillance particularly in patients with cirrhosis, advanced fibrosis or chronic hepatitis. Factor IX inhibitor development was not observed in the pivotal programme.
Nobody counted how many people took this and were fine, so this cannot be turned into a rate.
HOPE-B: Trial of AMT-061 in Severe or Moderately Severe Hemophilia B Patients (NCT03569891) · a recorded source, not a stored snapshot
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
Recombinant AAV5 vector, single intravenous infusion
✎ 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
Corticosteroid is reserved for reactive management of transaminase elevation.
✎ Source-linked record
Where this came from
A person wrote this into the record with the study named beside it. No reviewer has signed it off.
Recorded notes on which forms are sold and how they compare.
No source is stored against this line.
What is recorded as being sold
1 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 · 35b2db65-4c6c-4173-ab56-b2bca69193bd · read 2026-08-29
Those labels are classed as human prescription drug.
US prescribing information · 35b2db65-4c6c-4173-ab56-b2bca69193bd · read 2026-08-29
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 Etranacogene dezaparvovec 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 the effect is lifelong — five years is the measured horizon and hepatocytes do turn over
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 unblinded within-patient bleeding comparison is equivalent to a randomised blinded one
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 $3.5 million price is offset, which requires projecting factor IX savings decades beyond the measured five years
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 hepatocellular carcinoma question is closed for the class; low-rate AAV integration keeps hepatic surveillance a standing requirement
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.
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.
HOPE-B: annualised bleeding rate fell 64% against each patient's own prophylaxis
In plain words
Fifty-four men spent at least six months on standard prophylaxis first, so their own bleeding rate was measured before treatment. After one infusion, bleeds fell by roughly two thirds.
What was measured
Annualised bleeding rate 4.19 during lead-in versus 1.51 after treatment; rate ratio 0.36
Effect estimate
No reviewed effect estimate exists for this record.
Limits
See the technical detail.
From the source
Open-label phase 3 study with a lead-in period of at least six months of factor IX prophylaxis, then a single 2 x 10^13 gc/kg infusion in 54 men with factor IX activity 2% or less, enrolled regardless of pre-existing AAV5 neutralising antibodies. The annualised bleeding rate fell from 4.19 (95% CI 3.22 to 5.45) during lead-in to 1.51 (95% CI 0.81 to 2.82) during months 7 through 18, a rate ratio of 0.36 (95% Wald CI 0.20 to 0.64; P<0.001), establishing both non-inferiority against the 1.8 margin and superiority. Factor IX activity rose by a least-squares mean of 36.2 percentage points at 6 months and 34.3 at 18 months, and factor IX concentrate use fell by a mean 248,825 IU per participant per year (P<0.001 for all three). No treatment-related serious adverse events occurred.
Written into the record, not signed off as a reviewed claim
Five-year factor IX activity of 36.1 IU/dL — durability that did not decay
In plain words
Five years after a single infusion, average clotting factor levels were essentially where they had been at eighteen months. That is the result this whole field has been trying to produce.
What was measured
Mean factor IX activity at 5 years: 36.1 ± 15.7 IU/dL
Effect estimate
No reviewed effect estimate exists for this record.
Limits
See the technical detail.
From the source
Prespecified five-year analysis of all 54 participants. The adjusted annualised bleeding rate for all bleeds was 4.16 during lead-in and 1.52 during months 7 through 60, a 63% reduction (95% CI 24 to 82). Mean factor IX activity at five years was 36.1 ± 15.7 IU per deciliter. Mean exogenous factor IX consumption fell 96%, from 257,339 IU per year in lead-in to 10,924 IU per year post-treatment. Efficacy did not differ substantially between participants with and without baseline AAV5 neutralising antibodies. Treatment-related adverse events were rare after month 6.
Written into the record, not signed off as a reviewed claim
Pre-existing AAV5 antibodies were expected to disqualify patients, and mostly did not
In plain words
Most gene therapies exclude anyone whose immune system has already met the virus shell. This trial enrolled them anyway, and the treatment still worked below a certain antibody level.
What was measured
Not recorded
Effect estimate
No reviewed effect estimate exists for this record.
Limits
See the technical detail.
From the source
HOPE-B enrolled participants regardless of pre-existing AAV5 neutralising antibody status, a deliberate departure from the field's standard exclusion. Benefit and safety were observed in participants with predose titres below 700, and the five-year analysis found efficacy did not differ substantially between antibody-positive and antibody-negative participants. The contrast with the competing haemophilia B product is stark: in BENEGENE-2, 188 of 316 men screened (59.5%) were ineligible because of anti-AAV neutralising antibodies. Capsid choice and screening policy, not the transgene, decide who is treatable.
Written into the record, not signed off as a reviewed claim
A liver cancer case put the whole programme on FDA clinical hold in December 2020
In plain words
One participant developed liver cancer and the FDA halted the programme. A full genetic investigation concluded the therapy was unlikely to have caused it — but the hold happened, and the question it raised has not gone away for the field.
What was measured
Not recorded
Effect estimate
No reviewed effect estimate exists for this record.
Limits
This entry records a failure.
From the source
In December 2020 the FDA placed a clinical hold on the programme after a serious adverse event of hepatocellular carcinoma in a HOPE-B participant. The patient had multiple independent risk factors: prior hepatitis B and C, evidence of non-alcoholic fatty liver disease, a smoking history, a family history of cancer and advanced age. Independent molecular characterisation and vector integration analysis of the tumour and adjacent tissue supported the conclusion that the carcinoma was unrelated to treatment, and whole genome sequencing showed chromosome 1 and 8 abnormalities characteristic of hepatocellular carcinoma along with TP53 and other oncogenic mutations. The hold was lifted and the programme completed. AAV genomes are predominantly episomal but integrate at a low rate, so hepatic malignancy surveillance after liver-directed AAV is a permanent feature of this class rather than a resolved question.
Source
ASH Clinical News, reporting the independent investigation of the HOPE-B hepatocellular carcinoma case
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
The comparator was each patient's own unblinded lead-in, not a randomised arm
In plain words
There was no control group. Every participant was compared with their own bleeding rate from the months before treatment, and everyone knew who had been treated.
What was measured
That an unblinded within-patient bleeding-rate comparison carries the same weight as a randomised blinded one
Effect estimate
No reviewed effect estimate exists for this record.
Limits
See the technical detail.
From the source
HOPE-B is open-label and single-group. The lead-in design is a genuine strength — it establishes each patient's own prophylaxis-era bleeding rate prospectively rather than by recall — but it cannot control for regression to the mean, for the behavioural effect of knowing one has been treated, or for changes in bleed reporting once weekly infusions stop. Annualised bleeding rate is patient-reported and adjudicated, not instrumented. Factor IX activity, by contrast, is a laboratory measurement and is not vulnerable to any of this.
Written into the record, not signed off as a reviewed claim
A $3.5 million price justified by lifetime factor costs that were never measured against it
In plain words
The price was set on the argument that a lifetime of clotting factor costs more. The trial measured five years, and the arithmetic beyond that is a projection.
What was measured
That five years of measured factor IX savings establishes lifetime cost offset at the launch price
Effect estimate
No reviewed effect estimate exists for this record.
Limits
See the technical detail.
From the source
CSL Behring set a US list price of $3.5 million on approval in November 2022, making it the most expensive medicine in the world at the time. The offsetting-cost argument rests on measured factor IX consumption — 257,339 IU per participant per year during lead-in, falling 96% to 10,924 IU — extrapolated across a lifetime. The measured horizon is five years. No peer-reviewed cost of goods for the product exists, so no markup can be stated, and this page states none.
Source
Fierce Pharma, 22 November 2022 (list price); HOPE-B five-year factor IX consumption data
Role in the trial
Not matched to a registered study
Identity check
no open identity hold
Audit mark
caution
Review state
Written into the record, not signed off as a reviewed claim
Where else this substance is registered
FDA substance identifier (UNII)
Z5XCD5Q9RL
CAS registry number
2156583-26-3
WHO international nonproprietary name list entry
10963
EMA substance identifier
300000005896
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Trial roles classified for highlighted evidence
No registered study is classified as testing this substance.
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Safety mode resolved
The identity record classes it as CRISPR / Gene Therapy.
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Canonical metadata present
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What is missing or unclear◇Read from sources, not yet reviewed
What to learn next
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What is not here
8 questions this page could not answer
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How close this is to real life — found nothing in the sources checked.
Felt, measured, or meaningful — found nothing in the sources checked.
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What it may clash with — found nothing in the sources checked.
Other ways to the same goal — found nothing in the sources checked.
How this medicine reached us — found nothing in the sources checked.
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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 single AAV5 infusion carrying the hyperactive factor IX Padua variant: the annualised bleeding rate fell 64% against each patient's own prophylaxis lead-in, and at five years mean factor IX activity was still 36.1 IU/dL — the strongest durability result any liver-directed gene therapy has published.
Recorded evidence blocks (3)
Q1
On the Etranacogene dezaparvovec label: indicated for what?
"HEMGENIX is indicated for treatment of adults with Hemophilia B (congenital Factor IX deficiency) who: Currently use Factor IX prophylaxis therapy, or Have current or historical life-threatening hemorrhage, or Have repeated, serious spontaneous bleeding episodes. HEMGENIX is an adeno-associated virus vector-based gene…": indications and usage on Etranacogene dezaparvovec's label. DailyMed label · 35b2db65-4c6c-4173-ab56-b2bca69193bd · 2026-05-01
Q2
6 registered trials of Etranacogene dezaparvovec — at which phases?
ChEMBL 37 — CC BY-SA 3.0 Unported · ChEMBL ATC CC BY-SA · ClinicalTrials.gov — US Government work · mixed register set; per-register licences in docs/specs/corpus-20k-sources.md · openFDA / DailyMed — US Government work
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