This page shows what was measured, who it was measured in, and what that does not settle.
What Onasemnogene abeparvovec does in the body
Spinal muscular atrophy in babies under two
Motor neurons need a protein called SMN to stay alive. Your child's copies of the gene that makes it are broken. A harmless virus shell, chosen because it can cross from the bloodstream into the nervous system, carries a working copy of the gene into those neurons. It does not join the child's chromosomes; it sits alongside them as a separate loop of DNA and starts making the missing protein. Motor neurons that have not yet died can then survive. The ones already lost do not come back, which is why timing decides almost everything.
What happened in people
13 of 22 infants achieved independent sitting for 30 seconds or longer at 18 months, versus 0 of 23 untreated
✎ 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 a single infusion produces lifelong expression — the genome is episomal, re-dosing has never been evaluated, and anti-AAV9 antibodies foreclose a second attempt
Where it acts
Spinal cord anterior horn motor neurons, reached by systemic AAV9
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 structurallydiverse.
FDA substance registry · MLU3LU3EVV · read 2026-08-29
The material is recorded as coming from virus.
FDA substance registry · MLU3LU3EVV · 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 124 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.
Coprimary: independent sitting for 30 seconds or longer at 18 months, and survival free of permanent ventilation at 14 months
✓ The study showed what it set out to show
Who was studied
STR1VE (NCT03306277)
How many people
22
Study design
Phase 3, open label, single arm
Compared against
Not recorded for this study
Kind of result
Living longer, or avoiding a major event
What was found
P < 0.0001 for both coprimary endpoints versus the PNCR natural history cohort
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. Every patient had at least one adverse event, most commonly pyrexia. Serious events included bronchiolitis, pneumonia, respiratory distress and RSV bronchiolitis. Three serious events were treatment-related or possibly related: two elevated hepatic aminotransferases and one hydrocephalus.
How far it carries. This study is recorded from the curated record, not from the registry match.
Form and route. Recombinant AAV9 vector, single intravenous infusion
Interval reported. Not recorded in this summary
Written into the record, not signed off as a reviewed claim.
STR1VE: Gene Replacement Therapy Clinical Trial for Participants With SMA Type 1 (NCT03306277) · a recorded source, not a stored snapshot
Safety; secondary endpoint time to death or permanent ventilatory assistance
✓ The study showed what it set out to show
Who was studied
START (NCT02122952)
How many people
15
Study design
Phase 1, open label, dose escalation
Compared against
Not recorded for this study
Kind of result
Living longer, or avoiding a major event
What was found
Not reported as a p-value — descriptive comparison against historical cohorts
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. Elevated serum aminotransferases in 4 of 15 patients, attenuated by prednisolone. This early signal is the origin of the boxed warning added later.
How far it carries. This study is recorded from the curated record, not from the registry match.
Form and route. Recombinant AAV9 vector, single intravenous infusion
Interval reported. Not recorded in this summary
Written into the record, not signed off as a reviewed claim.
P = 0.0074; least-squares mean difference 1.88 (95% CI 0.51 to 3.25)
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. Sensory symptoms in 2 of 75 treated participants and 1 of 51 sham participants. Transaminase increases infrequent, mostly low grade and transient.
How far it carries. This study is recorded from the curated record, not from the registry match.
Form and route. Recombinant AAV9 vector, single intravenous infusion
Interval reported. 95% CI 0
Written into the record, not signed off as a reviewed claim.
STR1VE: Gene Replacement Therapy Clinical Trial for Participants With SMA Type 1 (NCT03306277) · a recorded source, not a stored snapshot
What we know
RNAWiki holds 3 written-up human studies for this substance, each with the question it asked.
How we know it
Each card names the study, the number of people and what the study set out to measure.
What this does not prove
These summaries were written by a person and have not been signed off as reviewed claims.
Why it matters
A study that failed is as informative as one that worked, and both are here.
What we still do not know
No reviewed claim exists, so no exact population, effect size or interval is published yet.
What 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
Onasemnogene abeparvovec
What a person takes: Recombinant AAV9 vector, single intravenous infusion.
The measurement behind this step
One intravenous infusion of 1.1 x 10^14 vector genomes per kg over 60 minutes, supplied as a kit of 2 to 14 single-use vials at a nominal 2.0 x 10^13 vg/mL. Systemic corticosteroid begins one day before and continues for 30 days, followed by a graded 28-day taper. Infusion is postponed in any child with an active infection.
Getting in
One intravenous infusion, under steroid cover
The dose goes into a vein over an hour. A steroid is started the day before and continued for a month, because the immune system reacts to the viral shell and that reaction is what damages the liver.
╌╌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 weight-based dose of 1.1 x 10^14 vg/kg is infused over 60 minutes, with prednisolone-equivalent 1 mg/kg/day beginning one day before and continuing 30 days. Children with pre-existing anti-AAV9 antibodies were excluded from the clinical programme because neutralising antibody blocks transduction.
AAV9 crosses out of the blood and into the nervous system
Most viral shells cannot get from the bloodstream into the brain and spinal cord. This one can, which is the whole reason it was chosen.
╌╌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
Serotype 9 was selected for its capacity to traverse the blood-brain barrier after systemic administration and transduce spinal cord anterior horn motor neurons, alongside high hepatic and cardiac uptake that accounts for the liver and troponin signals on the label.
The genome stays beside the chromosomes, not inside them
The delivered gene forms a separate loop of DNA in the nucleus. It is not stitched into the child's own chromosomes, so it cannot disrupt a neighbouring gene.
╌╌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 self-complementary genome persists predominantly as a non-integrating nuclear episome, bypassing the rate-limiting second-strand synthesis step of conventional single-stranded AAV. Absence of integration is why there is no insertional-oncogenesis boxed warning, and episomal dilution in dividing cells is why durability depends on the target being post-mitotic.
The hybrid promoter drives the gene continuously, so the neuron produces the protein it has been missing since before birth.
──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
A cytomegalovirus enhancer / chicken beta-actin hybrid promoter drives constitutive transcription of human SMN. Restoring SMN supports small nuclear ribonucleoprotein assembly and the motor-neuron-specific functions whose loss drives degeneration.
Neurons that were still alive at the time of infusion survive, and children gain abilities the disease would have taken. The neurons already lost do not come back.
╌╌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 STR1VE, 13 of 22 achieved independent sitting for 30 seconds or longer at 18 months versus 0 of 23 untreated, and 20 of 22 survived free of permanent ventilation at 14 months versus 6 of 23. The gradient between these results, the pre-symptomatic newborn-screening population, and the 1.88-point HFMSE gain in older children given the intrathecal product is the clearest evidence in the field that this drug preserves motor neurons rather than replacing them.
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.
Babies under two years old with genetically confirmed bi-allelic SMN1 mutations. Newborn screening has changed who this actually means: most children now identified are pre-symptomatic, a population the pivotal trial did not study.
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 of ITVISMA have not been established in pediatric patients younger than 2 years of age.”
US prescribing information · ab2e1c6c-4f95-4243-9296-1734e0a30591 · read 2026-08-30
On people who are pregnant, the label states: “Risk Summary There are no clinical studies in pregnant women to inform a product-associated risk.”
US prescribing information · ab2e1c6c-4f95-4243-9296-1734e0a30591 · read 2026-08-30
On people who are breastfeeding, the label states: “Risk Summary There is no information available on the presence of ITVISMA in human milk, the effects on the breastfed infant or the effects on milk production.”
US prescribing information · ab2e1c6c-4f95-4243-9296-1734e0a30591 · read 2026-08-30
On people with reduced liver function, the label states: “Patients with preexisting hepatic impairment or acute hepatic viral infection may be at higher risk of liver injury.”
US prescribing information · ab2e1c6c-4f95-4243-9296-1734e0a30591 · read 2026-08-30
Where the result stopped carrying
Manipulated animal product-testing data in the approval application, disclosed by the FDA on 6 August 2019 and known to the manufacturer before approval
Fatal acute liver failure in two patients reported in 2022, producing the current boxed warning language
Thrombotic microangiopathy, which the label warns can be life-threatening or fatal
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 AAV9 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. 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
0 x 10^13 vg/mL. Systemic corticosteroid begins one day before and continues for 30 days, followed by a graded 28-day taper. Infusion is postponed in any child with an active infection.
✎ 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
Boxed warning for serious liver injury and acute liver failure, including fatal cases. Further labelled warnings cover systemic immune response, thrombocytopenia, thrombotic microangiopathy which can be fatal, elevated cardiac troponin I, infusion-related reactions, and a theoretical risk of tumorigenicity from AAV vector DNA integration. The most common adverse reactions at 5% or more are elevated aminotransferases and vomiting.
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
Recombinant AAV9 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
0 x 10^13 vg/mL. Systemic corticosteroid begins one day before and continues for 30 days, followed by a graded 28-day taper. Infusion is postponed in any child with an active infection.
✎ Source-linked record
Where this came from
A person wrote this into the record with the study named beside it. No reviewer has signed it off.
Recorded notes on which forms are sold and how they compare.
No source is stored against this line.
What is recorded as being sold
1 product lists this as an active ingredient in the United States drug directory. 1 of them contain it and nothing else.
FDA National Drug Code directory · 71894-200 · read 2026-08-29
They are sold as injection, suspension, taken intrathecal.
FDA National Drug Code directory · 71894-200 · 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 · ab2e1c6c-4f95-4243-9296-1734e0a30591 · read 2026-08-29
Those labels are classed as human prescription drug.
US prescribing information · ab2e1c6c-4f95-4243-9296-1734e0a30591 · read 2026-08-29
ITVISMA is intrathecal at 3 DOSAGE FORMS AND STRENGTHS ITVISMA is a clear to slightly opaque, colorless to faint white suspension for intrathecal injection., recorded as fda label in effect 2026-06-16 in the United States.
US prescribing information · ab2e1c6c-4f95-4243-9296-1734e0a30591 · 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 Onasemnogene abeparvovec 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 a single infusion produces lifelong expression — the genome is episomal, re-dosing has never been evaluated, and anti-AAV9 antibodies foreclose a second attempt
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 historical-cohort comparison measures the treatment effect as precisely as a randomised control would
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 results in symptomatic infants transfer to the pre-symptomatic newborn-screened population that now dominates real-world use, or to older children
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 "cure" is the demonstrated claim, when motor neurons already lost at the time of infusion are not recovered
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 Onasemnogene abeparvovec 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.
STR1VE: 13 of 22 infants sat unassisted at 18 months, where 0 of 23 untreated infants did
In plain words
In babies under six months with the most severe form of the disease, more than half could sit up on their own for half a minute at eighteen months. In the untreated comparison group, none could.
What was measured
Independent sitting 30 seconds or longer at 18 months: 13/22 treated versus 0/23 untreated
Effect estimate
No reviewed effect estimate exists for this record.
Limits
See the technical detail.
From the source
Open-label, single-arm, single-dose phase 3 trial at 12 US sites; 22 patients younger than 6 months with biallelic SMN1 mutations and one or two SMN2 copies, dosed at 1.1 x 10^14 vg/kg. Coprimary endpoints: independent sitting for 30 seconds or longer at the 18-month visit, achieved by 13 of 22 (59%; 97.5% CI 36 to 100) versus 0 of 23 in the Pediatric Neuromuscular Clinical Research natural history cohort (P<0.0001); and survival free of permanent ventilation at 14 months, achieved by 20 of 22 (91%; 79 to 100) versus 6 of 23 (26%; 8 to 44) untreated (P<0.0001).
Written into the record, not signed off as a reviewed claim
The control group was a database, not a randomised arm
In plain words
Nobody was randomised. The children who got the drug were compared with records of children who had the disease before the drug existed.
What was measured
That a historical-cohort comparison quantifies the treatment effect as precisely as a randomised comparison would
Effect estimate
No reviewed effect estimate exists for this record.
Limits
See the technical detail.
From the source
Both pivotal studies are open-label and single-arm. STR1VE compared its 22 patients against 23 untreated infants drawn from the Pediatric Neuromuscular Clinical Research dataset; START compared 15 patients against published natural history. Historical comparison is defensible in a disease with a near-uniform fatal course, and the effect size here is large enough that confounding is an implausible full explanation. It is not the same evidence as a concurrent control, and it cannot separate the drug's contribution from improvements in supportive care over the intervening years.
Written into the record, not signed off as a reviewed claim
Boxed warning: acute liver failure with fatal outcomes has been reported
In plain words
Children have died of liver failure after this infusion. The warning is on the front of the label, and the liver monitoring runs for at least three months.
What was measured
Not recorded
Effect estimate
No reviewed effect estimate exists for this record.
Limits
This entry records a failure.
From the source
The US prescribing information carries a boxed warning for serious liver injury and acute liver failure, stating that cases of acute liver failure with fatal outcomes have been reported and that patients with pre-existing liver impairment may be at higher risk. Two fatal cases were reported by Novartis in 2022, occurring approximately six to seven weeks after infusion with hepatotoxicity presenting roughly one to ten days after the corticosteroid taper began; the patients were aged 4 months and 28 months. The label mandates liver assessment before infusion, systemic corticosteroid for 30 days with a graded taper, liver monitoring for at least three months, and specialist referral if abnormalities persist above twice the upper limit of normal.
Source
ZOLGENSMA US prescribing information, Boxed Warning and Sections 2.1, 2.3, 5.1
Role in the trial
Not matched to a registered study
Identity check
no open identity hold
Audit mark
caution
Review state
Written into the record, not signed off as a reviewed claim
The FDA disclosed that animal test data in the approval application had been manipulated
In plain words
A month after approving the drug, the FDA announced that the manufacturer had told it about manipulated data in animal product-testing submitted with the application — and that the manufacturer had known before approval.
What was measured
Not recorded
Effect estimate
No reviewed effect estimate exists for this record.
Limits
See the technical detail.
From the source
On 6 August 2019 the FDA issued a public statement: on 28 June 2019, after the 24 May 2019 approval, AveXis informed the agency of a data manipulation issue affecting the accuracy of certain animal product-testing data in the biologics licence application. The FDA said its concerns were limited to a portion of product testing data used to develop the manufacturing process, that the data did not change its positive assessment of the human clinical trials, and that Zolgensma should remain on the market, while stating that the integrity of the product testing data remained a matter it was assessing. Two senior AveXis executives were terminated. No regulatory action was ultimately taken against the company.
Source
FDA Statement on data accuracy issues with recently approved gene therapy, 6 August 2019
Role in the trial
Not matched to a registered study
Identity check
no open identity hold
Audit mark
contested
Review state
Written into the record, not signed off as a reviewed claim
START: all 15 infants alive and event-free at 20 months against 8% historical survival
In plain words
The first-in-human study treated fifteen babies. All were alive and off permanent ventilation at twenty months, where historically about 8 in 100 would have been. Two of them walked.
What was measured
Survival free of permanent ventilation at 20 months: 15/15 versus 8% historical
Effect estimate
No reviewed effect estimate exists for this record.
Limits
See the technical detail.
From the source
Phase 1, open-label, dose-escalation: 3 patients at 6.7 x 10^13 vg/kg and 12 at 2.0 x 10^14 vg/kg. As of the 7 August 2017 data cutoff, all 15 were alive and event-free at 20 months of age against a historical survival rate of 8%. In the high-dose cohort, CHOP INTEND rose 9.8 points at one month and 15.4 points at three months from baseline, against a decline in historical cohorts; 11 of 12 sat unassisted, 9 rolled over, 11 fed orally and could speak, and 2 walked independently. Elevated serum aminotransferases occurred in 4 patients and were attenuated by prednisolone — the first signal of the toxicity that later became a boxed warning.
Written into the record, not signed off as a reviewed claim
The intrathecal version reached older patients in 2025 — with a much smaller measured effect
In plain words
A version injected into the spinal fluid was approved in November 2025 for patients aged two and over. It beat a sham procedure, but by under two points on a 66-point motor scale.
What was measured
HFMSE change at week 52, least-squares mean difference versus sham: 1.88 points
Effect estimate
No reviewed effect estimate exists for this record.
Limits
See the technical detail.
From the source
STEER (NCT05089656) randomised 126 treatment-naive patients aged 2 to under 18 who could sit but had never walked, to intrathecal onasemnogene abeparvovec (n=75) or a sham procedure (n=51), double-blind for 52 weeks. The primary endpoint, change from baseline in the Hammersmith Functional Motor Scale-Expanded, favoured treatment with a least-squares mean difference of 1.88 (95% CI 0.51 to 3.25; P=0.0074). Two treated participants and one sham participant developed sensory symptoms. Itvisma (onasemnogene abeparvovec-brve) was approved by the FDA on 24 November 2025 for patients aged 2 and older. The contrast with the infant data is the point: the same vector and transgene produce a transformative result in a pre-symptomatic newborn and a modest one in a child whose motor neurons are already gone.
Written into the record, not signed off as a reviewed claim
Durability is a promise about a non-integrating genome that has never been re-dosed
In plain words
The gene does not join the child's chromosomes — it sits beside them. Whether it keeps working as the child grows has not been established, and the label says repeat dosing has never been tested.
What was measured
That a single infusion in infancy produces lifelong SMN expression, when no re-dosing option exists if it does not
Effect estimate
No reviewed effect estimate exists for this record.
Limits
See the technical detail.
From the source
The AAV9 genome persists mainly as a non-integrating episome. Episomes are diluted by cell division, so durability depends on the target cell being post-mitotic — which motor neurons are, and hepatocytes and cardiomyocytes are not. The label's Limitations of Use state that the safety and effectiveness of repeat administration have not been evaluated and that use in patients with advanced SMA has not been evaluated. A second dose is in any case obstructed by the anti-AAV9 antibodies the first dose induces. Warnings also list a theoretical risk of tumorigenicity from AAV vector DNA integration, with a request to report any tumours.
Source
ZOLGENSMA US prescribing information, Limitations of Use and Section 5.6
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)
MLU3LU3EVV
CAS registry number
1922968-73-7
WHO international nonproprietary name list entry
10619
RxNorm concept
2170226
EMA substance identifier
100000177723
DrugBank
DB15528
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How this medicine reached us
Kept near the foot of the page. A historical event moves up only when it changes something about this substance today.
What the approval register records
The earliest marketing start date recorded for a listed product is 20251124.
FDA National Drug Code directory · 71894-200 · read 2026-08-29
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A single intravenous AAV9 infusion delivering a working SMN1 gene: 13 of 22 infants sat unassisted for 30 seconds at 18 months where none of 23 untreated infants did, and 20 of 22 survived to 14 months without permanent ventilation — measured against a historical cohort, not a randomised control, and carrying a boxed warning for fatal acute liver failure.
Recorded evidence blocks (5)
Q2
On the Onasemnogene abeparvovec label: indicated for what?
"ITVISMA is indicated for the treatment of spinal muscular atrophy (SMA) in adult and pediatric patients 2 years of age and older with confirmed mutation in survival motor neuron 1 (SMN1) gene. ITVISMA is an adeno-associated virus (AAV) vector-based gene therapy indicated for the treatment of spinal muscular atrophy…": indications and usage on Onasemnogene abeparvovec's label. DailyMed label · ab2e1c6c-4f95-4243-9296-1734e0a30591 · 2026-06-16
Q3
8 registered trials of Onasemnogene abeparvovec — at which phases?
At the median, Onasemnogene abeparvovec's trials enrolled 33 people — anything larger?
Median enrolment
33
Largest enrolment
126
Registered trials counted
7
Q5
What do 559 spontaneous reports say about Onasemnogene abeparvovec — 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.
Onasemnogene abeparvovec appears in spontaneous reports to regulators. Across the 10 most-reported reaction terms, 559 reaction mentions were counted: pyrexia 91; aspartate aminotransferase increased 80; alanine aminotransferase increased 74; vomiting 70. FAERS via Open Targets · CHEMBL4297240 · 2026-06-24
Show the evidence
pyrexia
91
aspartate aminotransferase increased
80
alanine aminotransferase increased
74
vomiting
70
hepatic enzyme increased
50
thrombocytopenia
49
4 more recorded rows
platelet count decreased
42
liver function test increased
38
troponin i increased
35
transaminases increased
30
recorded 2026-06-24 · last checked 2026-09-04
Q6
Which 10 reactions does Onasemnogene abeparvovec's label not list?
alanine aminotransferase increased, aspartate aminotransferase increased and hepatic enzyme increased and 7 more reported for Onasemnogene abeparvovec, absent from its label. FAERS via Open Targets · CHEMBL4297240 · 2026-06-24
2 label terms; 10 reported and unlisted; ab2e1c6c-4f95-4243-9296-1734e0a30591
Show the evidence
alanine aminotransferase increased
count not stated
aspartate aminotransferase increased
count not stated
hepatic enzyme increased
count not stated
liver function test increased
count not stated
platelet count decreased
count not stated
pyrexia
count not stated
4 more recorded rows
thrombocytopenia
count not stated
transaminases increased
count not stated
troponin i increased
count not stated
vomiting
count not stated
recorded 2026-06-24 · last checked 2026-09-04
Where it is registeredIdentifiers, relations and other names
Onasemnogen abeparvovec, Zolgensma, oa, NON-REPLICATING RECOMBINANT SELF-COMPLEMENTARY (SC) ADENO-ASSOCIATED VIRUS SEROTYPE 9 (AAV9) VECTOR CONTAINING THE CDNA OF THE SURVIVAL OF MOTOR NEURON 2 (SMN2) GENE UNDER THE CONTROL OF THE HYBRID CYTOMEGALOVIRUS (CMV) ENHANCER/CHICKEN BETA-ACTIN PROMOTER (CBA), ONASEMNOGENE ABEPARVOVEC [MI], ONASEMNOGENE ABEPARVOVEC [USAN], Onasemnogene abeparvovec [WHO-DD], onasemnogene abeparvovec [INN]
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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