This page shows what was measured, who it was measured in, and what that does not settle.
What Exagamglogene autotemcel does in the body
Sickle cell disease and transfusion-dependent beta-thalassemia
Before you were born you made a different kind of haemoglobin that does not sickle and does not depend on the broken gene. After birth a switch turned it off. Doctors collect your own blood stem cells, and in the laboratory CRISPR makes one cut in the switch so the cell can no longer read it. Your own repair machinery seals the cut imperfectly, which is the point: the switch is now broken. Chemotherapy empties your bone marrow, the edited cells go back in, and every red cell they make from then on carries fetal haemoglobin.
What happened in people
29 of 30 evaluable sickle cell patients (97%; 95% CI 83 to 100) free of severe vaso-occlusive crises for at least 12 consecutive months
✎ 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.
CLIMB SCD-121: A Safety and Efficacy Study Evaluating CTX001 in Severe Sickle Cell Disease (NCT03745287) · a recorded source, not a stored snapshot
The limit that matters most
The rate-limiting step in practice is authorised transplant centre capacity and payer arrangement, not manufacturing
Where it acts
Bone marrow — autologous CD34+ haematopoietic stem and progenitor cells
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 · S53L777GM8 · read 2026-08-29
It is recorded as coming from HOMO SAPIENS WHOLE. The part recorded is bone-marrow.
FDA substance registry · S53L777GM8 · 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 128 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.
Biomarker
A biomarker is a number from a test that stands in for something about health.
A picture of it, and where the picture fails
A biomarker is like a fuel gauge.
Where that stops being true. A gauge is wired to the tank. Many biomarkers are only loosely tied to health.
What people get wrong. A better number is read as a better life. Several medicines improved a number and helped nobody.
A measurable indicator used as a substitute for a clinical outcome of interest.
Placebo
A placebo is a dummy treatment given so the real one can be compared with it.
A picture of it, and where the picture fails
A placebo is like a blank control in an experiment.
Where that stops being true. A blank does nothing. People given a placebo often do get better.
What people get wrong. A placebo effect is read as imaginary. The improvement is measured and real.
An inactive intervention matched in appearance to the test intervention, used to control for non-specific effects.
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.
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.
Freedom from severe vaso-occlusive crises for at least 12 consecutive months
✓ The study showed what it set out to show
Who was studied
CLIMB SCD-121 (NCT03745287)
How many people
44
Study design
Phase 2/3, single group, open label
Compared against
Not recorded for this study
Kind of result
A number that stands in for health
What was found
P < 0.001 against a null hypothesis of 50% response
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. Safety profile dominated by busulfan myeloablation rather than by the edit. No cancers observed, but median follow-up was 19.3 months, far short of the timescale on which insertional or off-target oncogenesis would be expected to declare itself.
How far it carries. This study is recorded from the curated record, not from the registry match.
Form and route. Ex vivo CRISPR-Cas9 edited autologous CD34+ cell suspension, single intravenous infusion
Interval reported. Not recorded in this summary
Written into the record, not signed off as a reviewed claim.
CLIMB SCD-121: A Safety and Efficacy Study Evaluating CTX001 in Severe Sickle Cell Disease (NCT03745287) · a recorded source, not a stored snapshot
CLIMB THAL-111: A Safety and Efficacy Study Evaluating CTX001 in Transfusion-Dependent Beta-Thalassemia (NCT03655678) · a recorded source, not a stored snapshot
Transfusion independence: weighted average haemoglobin at least 9 g/dL without red-cell transfusion for at least 12 consecutive months
✓ The study showed what it set out to show
Who was studied
CLIMB THAL-111 (NCT03655678)
How many people
52
Study design
Phase 2/3, single group, open label
Compared against
Not recorded for this study
Kind of result
A number that stands in for health
What was found
P < 0.001 against a null hypothesis of 50% response
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. No deaths or cancers. Grade 3-4 cytopenias near-universal, attributable to conditioning.
How far it carries. This study is recorded from the curated record, not from the registry match.
Form and route. Ex vivo CRISPR-Cas9 edited autologous CD34+ cell suspension, single intravenous infusion
Interval reported. Not recorded in this summary
Written into the record, not signed off as a reviewed claim.
CLIMB SCD-121: A Safety and Efficacy Study Evaluating CTX001 in Severe Sickle Cell Disease (NCT03745287) · a recorded source, not a stored snapshot
CLIMB THAL-111: A Safety and Efficacy Study Evaluating CTX001 in Transfusion-Dependent Beta-Thalassemia (NCT03655678) · 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
Exagamglogene autotemcel
What a person takes: Ex vivo CRISPR-Cas9 edited autologous CD34+ cell suspension, single intravenous infusion.
The measurement behind this step
One intravenous infusion of the patient's own gene-edited haematopoietic stem cells, at a minimum of 3 x 10^6 CD34+ cells/kg, given 48 hours to 7 days after full myeloablative busulfan conditioning. Each vial is infused within 20 minutes of thaw and no in-line blood filter is used. The whole course — mobilisation, apheresis, manufacture, conditioning, infusion, engraftment — runs to months, not to a single appointment.
Getting in
Your own stem cells are collected
A drug pushes blood stem cells out of the bone marrow into the bloodstream, and a machine filters them out over several sessions. Nothing has been changed yet.
╌╌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
Plerixafor-mobilised autologous CD34+ haematopoietic stem and progenitor cells are collected by apheresis and immunomagnetically selected. Granulocyte colony-stimulating factor is contraindicated for mobilisation in sickle cell disease because of the risk of precipitating a vaso-occlusive crisis.
CLIMB SCD-121: A Safety and Efficacy Study Evaluating CTX001 in Severe Sickle Cell Disease (NCT03745287) · a recorded source, not a stored snapshot
Reaching the cell
CRISPR is delivered as a protein, not as a gene
The editing machine is pushed into the cells by a brief electric pulse. It is a protein, so the cell breaks it down within days — nothing is left behind that keeps cutting.
╌╌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 recombinant SpCas9 protein pre-complexed with a chemically modified single guide RNA is electroporated into the CD34+ cells as a ribonucleoprotein. There is no viral vector and no integrating DNA, which is the structural reason this product carries no insertional-oncogenesis boxed warning.
CLIMB SCD-121: A Safety and Efficacy Study Evaluating CTX001 in Severe Sickle Cell Disease (NCT03745287) · a recorded source, not a stored snapshot
What it acts on
One cut in the switch that silences fetal haemoglobin
The guide leads the scissors to a specific stretch of DNA that acts as a volume control for the off-switch, and makes a single cut there.
╌╌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 guide directs a double-strand break at the +58 erythroid-specific enhancer of BCL11A. The coding sequence of BCL11A is untouched; only the enhancer that drives its expression in the red-cell lineage is targeted, which preserves BCL11A function in the B-lymphoid and neural lineages where it is required.
CLIMB SCD-121: A Safety and Efficacy Study Evaluating CTX001 in Severe Sickle Cell Disease (NCT03745287) · a recorded source, not a stored snapshot
The change it makes
The cell repairs the cut badly, and that is the treatment
The cell glues the ends back together and loses a few letters in the process. The enhancer no longer works, so the off-switch is no longer made in red cells.
╌╌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
Non-homologous end joining introduces insertions and deletions at the cut site, disrupting the GATA1 motif within the enhancer. Erythroid BCL11A expression falls, gamma-globin transcription from HBG1 and HBG2 is derepressed, and fetal haemoglobin production resumes.
CLIMB SCD-121: A Safety and Efficacy Study Evaluating CTX001 in Severe Sickle Cell Disease (NCT03745287) · a recorded source, not a stored snapshot
What that does for a person
Fetal haemoglobin in nearly every red cell
After chemotherapy clears the old marrow, the edited cells take root and make red cells full of fetal haemoglobin, which does not sickle and does not need the broken 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
In CLIMB THAL-111, mean total haemoglobin during transfusion independence was 13.1 g/dL with fetal haemoglobin 11.9 g/dL, distributed pancellularly across at least 94% of red cells. Pancellular distribution matters more than the mean: a high average concentrated in a minority of cells would leave the rest still sickling.
CLIMB SCD-121: A Safety and Efficacy Study Evaluating CTX001 in Severe Sickle Cell Disease (NCT03745287) · 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.
Patients aged 2 and older with severe disease — a history of recurrent vaso-occlusive crises, or transfusion dependence — who can survive full myeloablative chemotherapy and who have access to an authorised transplant centre.
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 CASGEVY in pediatric patients aged less than 2 years have not been established.”
US prescribing information · 7c3e12ad-e2fe-4d3f-a630-ea7364d9e846 · read 2026-08-30
On older people, the label states: “CASGEVY has not been studied in patients > 65 years of age.”
US prescribing information · 7c3e12ad-e2fe-4d3f-a630-ea7364d9e846 · read 2026-08-30
On people who are pregnant, the label states: “Risk Summary There are no clinical data from the use of exagamglogene autotemcel during pregnancy.”
US prescribing information · 7c3e12ad-e2fe-4d3f-a630-ea7364d9e846 · read 2026-08-30
On people who are breastfeeding, the label states: “Risk Summary There are no data on the presence of exagamglogene autotemcel in human or animal milk, the effects on the breastfed child, or the effects on milk production.”
US prescribing information · 7c3e12ad-e2fe-4d3f-a630-ea7364d9e846 · read 2026-08-30
Where the result stopped carrying
Commercial access: a $2.2 million list price against a population concentrated in Medicaid produced near-zero uptake in the first year and prompted CMS to build a bespoke access model
Nothing in the pivotal efficacy programme failed; the failures in this class belong to delivery, not to the biology
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
Ex vivo CRISPR-Cas9 edited autologous CD34+ cell suspension, 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: S7.
No source is stored against this line.
What is in the pack
One intravenous infusion of the patient's own gene-edited haematopoietic stem cells, at a minimum of 3 x 10^6 CD34+ cells/kg, given 48 hours to 7 days after full myeloablative busulfan conditioning.
✎ 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. The rest of the recorded wording: Each vial is infused within 20 minutes of thaw and no in-line blood filter is used. The whole course — mobilisation, apheresis, manufacture, conditioning, infusion, engraftment — runs to months, not to a single appointment.
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. Labelled warnings are neutrophil engraftment failure, delayed platelet engraftment, hypersensitivity reactions, and off-target genome editing risk that cannot be ruled out. The dominant clinical toxicity is the conditioning: mucositis and febrile neutropenia at 25% or more, and grade 3-4 neutropenia, thrombocytopenia, leukopenia, anaemia and lymphopenia at 50% or more. Infertility from myeloablation is a foreseeable consequence and warrants a fertility discussion before conditioning.
Nobody counted how many people took this and were fine, so this cannot be turned into a rate.
CLIMB SCD-121: A Safety and Efficacy Study Evaluating CTX001 in Severe Sickle Cell Disease (NCT03745287) · 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
Ex vivo CRISPR-Cas9 edited autologous CD34+ cell suspension, 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
Each vial is infused within 20 minutes of thaw and no in-line blood filter is used. The whole course — mobilisation, apheresis, manufacture, conditioning, infusion, engraftment — runs to months, not to a single appointment.
✎ 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 · 51167-290 · read 2026-08-29
They are sold as injection, suspension, taken intravenous.
FDA National Drug Code directory · 51167-290 · 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 · 7c3e12ad-e2fe-4d3f-a630-ea7364d9e846 · read 2026-08-29
Those labels are classed as cellular therapy.
US prescribing information · 7c3e12ad-e2fe-4d3f-a630-ea7364d9e846 · read 2026-08-29
CASGEVY is intravenous at 3 DOSAGE FORMS AND STRENGTHS CASGEVY is a cell suspension for intravenous infusion., recorded as fda label in effect 2026-07-07 in the United States.
US prescribing information · 7c3e12ad-e2fe-4d3f-a630-ea7364d9e846 · 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 Exagamglogene autotemcel 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 permanent — the longest follow-up in either pivotal publication was 48.1 months, and the disease timescale is a lifetime
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 eliminating crises prevents stroke, nephropathy, pulmonary hypertension or cumulative organ damage; none was an endpoint
Why it sounds right. It follows from something real on this page: a body step, an animal result or a related finding.
The missing step. Nobody measured this in people for this use, or the study that did measure it did not show it.
What would change this
A study in people, for this exact use, measuring this exact thing, that a reviewer signs off.
RNAWiki has not yet published a reviewed conclusion for this use.
✗Goes past the evidence
That the absence of cancer over a median 19.3 months settles the off-target question, when the label states the risk cannot be ruled out
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 the demonstrated claim is twelve months of freedom from a symptom in a single-arm study
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 Exagamglogene autotemcel 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.
CLIMB SCD-121: 29 of 30 evaluable patients free of vaso-occlusive crises for 12 months or more
In plain words
Forty-four people with severe sickle cell disease were treated. Of the thirty followed long enough to judge, twenty-nine went at least a year with no severe pain crisis, and all thirty went a year with no hospital admission for one.
What was measured
Proportion free of severe vaso-occlusive crises for at least 12 consecutive months: 29/30 (97%)
Effect estimate
No reviewed effect estimate exists for this record.
Limits
See the technical detail.
From the source
Phase 3, single-group, open-label. Patients aged 12 to 35 with at least two severe vaso-occlusive crises in each of the two years before screening. 44 received exa-cel; median follow-up 19.3 months (range 0.8 to 48.1). Neutrophils and platelets engrafted in every patient. Of 30 evaluable, 29 (97%; 95% CI 83 to 100) were free of vaso-occlusive crises for at least 12 consecutive months and 30 (100%; 95% CI 88 to 100) were free of hospitalisation for one, P<0.001 for both against a null of 50% response. No cancers occurred.
Written into the record, not signed off as a reviewed claim
CLIMB THAL-111: transfusion independence in 32 of 35 evaluable thalassemia patients
In plain words
In transfusion-dependent beta-thalassemia, 91% of the patients followed long enough kept a haemoglobin of at least 9 g/dL for a year with no transfusions at all.
What was measured
Transfusion independence for at least 12 consecutive months: 32/35 (91%)
Effect estimate
No reviewed effect estimate exists for this record.
Limits
See the technical detail.
From the source
Phase 3, single-group, open-label, in patients aged 12 to 35 with beta0/beta0, beta0/beta0-like or non-beta0/beta0-like genotypes. 52 received exa-cel; median follow-up 20.4 months (range 2.1 to 48.1). Of 35 evaluable, 32 (91%; 95% CI 77 to 98; P<0.001 against a null of 50%) achieved transfusion independence. During independence, mean total haemoglobin was 13.1 g/dL and mean fetal haemoglobin 11.9 g/dL, with fetal haemoglobin distributed pancellularly across at least 94% of red cells. No deaths or cancers occurred.
Written into the record, not signed off as a reviewed claim
Off-target editing has not been ruled out, and the label says so
In plain words
CRISPR was designed to cut one place. Whether it also cut somewhere else in a particular person depends on that person's own genetic variants, and the label states plainly that the risk cannot be excluded.
What was measured
That a clean on-target edit in the reference genome implies no consequential off-target edit in this patient
Effect estimate
No reviewed effect estimate exists for this record.
Limits
See the technical detail.
From the source
Section 5.4 of the US prescribing information, added in August 2025, reads: "The risk of unintended, off-target editing in CD34+ cells due to genetic variants cannot be ruled out." Off-target assessment for this product is built on in-silico prediction and in-vitro nomination in reference genomes, which cannot enumerate the private variants of an individual patient near the guide site. No trial endpoint measured off-target editing in vivo, and the pivotal studies reported no cancers over a median follow-up under two years — an observation that constrains but does not settle a question whose natural timescale is decades.
Source
CASGEVY US prescribing information, Warnings and Precautions 5.4 (recent major change 08/2025)
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
Neither pivotal trial had a control group, and neither measured survival or organ damage
In plain words
Both studies compared each patient to their own history, not to a randomised comparison group, and neither asked whether patients live longer or keep their kidneys.
What was measured
That eliminating crises for twelve months is the same finding as preventing organ damage or extending life
Effect estimate
No reviewed effect estimate exists for this record.
Limits
See the technical detail.
From the source
CLIMB SCD-121 and CLIMB THAL-111 are single-group, open-label studies. The statistical test in each is against a fixed null response rate of 50%, not against a concurrent arm. Endpoints are freedom from vaso-occlusive crises and transfusion independence over 12 months. Stroke, silent cerebral infarct, nephropathy, pulmonary hypertension, cumulative organ damage and mortality were not endpoints. Median follow-up at publication was 19.3 and 20.4 months.
Written into the record, not signed off as a reviewed claim
The harms measured are mostly the harms of the chemotherapy, not of the edit
In plain words
The serious side effects in both trials looked like a bone marrow transplant, because the patient has one. The gene editing itself contributed little to the adverse event list.
What was measured
Grade 3-4 non-laboratory adverse reactions at 25% or more: mucositis, febrile neutropenia
Effect estimate
No reviewed effect estimate exists for this record.
Limits
See the technical detail.
From the source
Both publications describe the safety profile as generally consistent with myeloablative busulfan conditioning and autologous haematopoietic stem cell transplantation. The FDA label lists mucositis and febrile neutropenia as the most common grade 3 or 4 non-laboratory adverse reactions at 25% or more incidence, plus decreased appetite in sickle cell disease, and neutropenia, thrombocytopenia, leukopenia, anaemia and lymphopenia as grade 3 or 4 laboratory abnormalities at 50% or more. Warnings cover neutrophil engraftment failure, delayed platelet engraftment and hypersensitivity.
Source
CASGEVY US prescribing information, Sections 5 and 6; Frangoul 2024 and Locatelli 2024
Role in the trial
Not matched to a registered study
Identity check
no open identity hold
Audit mark
verified
Review state
Written into the record, not signed off as a reviewed claim
The licence moved from age 12 down to age 2, on later evidence
In plain words
At approval this was a medicine for teenagers and adults. It is now approved from age two, which is a different risk-benefit judgement about giving a child myeloablative chemotherapy.
What was measured
Not recorded
Effect estimate
No reviewed effect estimate exists for this record.
Limits
See the technical detail.
From the source
The original BLA (STN 125785) covered patients aged 12 and older with sickle cell disease with recurrent vaso-occlusive crises, approved 8 December 2023, extended to transfusion-dependent beta-thalassemia on 16 January 2024. A separate BLA (STN 125787) now covers patients aged 2 years and older for both indications, with approval letters dated 18 March 2026, 15 June 2026 and 1 July 2026 on the FDA product page. The Indications and Usage and Dosage and Administration sections of the label were revised in July 2026.
Source
FDA CASGEVY product page and approval letters (content current 2 July 2026)
Role in the trial
Not matched to a registered study
Identity check
no open identity hold
Audit mark
verified
Review state
Written into the record, not signed off as a reviewed claim
A $2.2 million list price met an eligible population that mostly could not reach it
In plain words
The therapy was priced at $2.2 million per patient in the United States. Uptake in the first year was close to nothing, not because the science failed but because the delivery system around it did.
What was measured
Not recorded
Effect estimate
No reviewed effect estimate exists for this record.
Limits
This entry records a failure.
From the source
Vertex and CRISPR Therapeutics set a US list price of $2.2 million on approval in December 2023; bluebird bio set $3.1 million for the competing product the same week. Reaching either requires an authorised transplant centre, weeks of inpatient myeloablative conditioning, and a payer willing to fund a single-payment therapy for a population disproportionately covered by Medicaid. The Centers for Medicare & Medicaid Services responded by building the Cell and Gene Therapy Access Model, an outcomes-based multi-state negotiation specifically for sickle cell gene therapy, with states beginning participation in 2025. A therapy whose access problem needs a new federal payment model is a therapy whose access problem is structural.
Source
Reuters, 8 December 2023 (list prices); CMS Cell and Gene Therapy Access Model
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)
S53L777GM8
RxNorm concept
2671671
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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 20231208.
FDA National Drug Code directory · 51167-290 · read 2026-08-29
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The first approved CRISPR medicine: it cuts the enhancer that silences fetal haemoglobin, and 29 of 30 evaluable sickle cell patients went at least twelve months without a severe crisis — measured over a median 19.3 months in a single-arm trial, not over a lifetime and not against a control group.
Recorded evidence blocks (4)
Q2
On the Exagamglogene autotemcel label: indicated for what?
"1. INDICATIONS AND USAGE CASGEVY is indicated for the treatment of patients aged 2 years and older with: sickle cell disease (SCD) with recurrent vaso-occlusive crises transfusion-dependent β - thalassemia (TDT) CASGEVY is an autologous genome edited hematopoietic stem cell-based gene therapy indicated for the…": indications and usage on Exagamglogene autotemcel's label. DailyMed label · 7c3e12ad-e2fe-4d3f-a630-ea7364d9e846 · 2026-07-07
Q3
8 registered trials of Exagamglogene autotemcel — at which phases?
exa-cel, Autologous CD34+ cells isolated from mobilised peripheral blood by positive selection, modified by CRISPR/Cas9 (clustered regularly interspaced short palindromic repeats/CRISPR-associated protein 9) mediated gene editing consisting of a guide RNA (gRNA) introduced transiently as ribonucleoprotein (RNP) complex, targeting the erythroid lineage-specific enhancer region of BCL11A (B-cell lymphoma/leukemia 11A). The site-specific cleavage by Cas9 forms a double strand break (DSB), which is subsequently repaired by nonhomologous end-joining (NHEJ), leading to the transcriptional repression of BCL11A, a repressor of γ-globin gene transcription, EXAGAMGLOGENE AUTOTEMCEL [USAN], Exagamglogene autotemcel [WHO-DD], exagamglogene autotemcel [INN]
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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