This page shows what was measured, who it was measured in, and what that does not settle.
What Mipomersen does in the body
Formerly used for an extremely severe inherited form of high cholesterol.
Every particle of bad cholesterol is built around one copy of a scaffolding protein called apolipoprotein B, and the liver makes it. Mipomersen shut down that production so fewer particles could be assembled and exported. The problem was what happened to the fat that could no longer leave: it stayed in the liver. Hepatic fat rose by ten percentage points in six months, and that is what ended the drug.
What happened in people
In 51 people, LDL, often called “bad” cholesterol, fell by about one quarter over 26 weeks.
✓ Reviewed first-read answer
Where this came from
A person wrote this and a reviewer approved it against this exact record. It carries no effect size.
A reviewer approved this against this record. The reviewed-claim record carrying the exact population and effect size does not exist yet.
No source is stored against this line.
The limit that matters most
No study showed that mipomersen prevented heart attacks.
Where it acts
Liver hepatocyte
Kind of result
A number that stands in for health
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 nucleicacid.
FDA substance registry · 9GJ8S4GU0M · read 2026-08-29
Its recorded molecular formula is C230H305N67O122P19S19-19, weighing 7158.
PubChem record · 71301230 · read 2026-08-29
Where each sentence above came from
No recorded sentence describes the change this makes in a way that stands on its own. The page opens with what it is taken for instead, and the recorded explanation follows below.
Shown as the opening line on this page.
The limit a reviewer approved as the one that matters most here.
The four opening statements run to 99 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.
Stand-in result
A stand-in result is a number measured because the real result takes too long.
A picture of it, and where the picture fails
It is like judging a journey by the speedometer rather than by arriving.
Where that stops being true. Speed does predict arrival. Many stand-in results do not predict the real one.
What people get wrong. A stand-in result is often reported as the result itself.
A surrogate endpoint substituted for a clinical endpoint, valid only where the substitution has been shown to hold.
What happened in people◇Read from sources, not yet reviewed
What was measured, goal by goal
One row for each goal a registered study measured something for. One column for each kind of thing that could be measured.
Registered studies list 8 outcome measures that RNAWiki could read. A registered study says what someone planned to measure. It does not say what they found. 0 of the matched studies tested this substance, and 0 posted a result.
There is no single score. A strong test result and a weak life result are different facts.
Goals down the side, kinds of measurement across the top. Each cell says what kind of thing was registered, not what was found.
Goal
Life outcome
What a body can do
How a person feels
A test result
A step in the body
Harms
How long
Who was studied
Cholesterol
∅Nothing in the sources checkedNo registered study lists a life outcome for this goal.
∅Nothing in the sources checkedNo registered study lists a performance measure for this goal.
∅Nothing in the sources checkedNo registered study lists a symptom measure for this goal.
△Only a number moved3 registered test measure.
∅Nothing in the sources checkedNo registered study lists a body-step measure for this goal.
—Not recordedHarms were not a registered measure for this goal.
—Not recordedNo finished study window is recorded.
…Waiting for a reviewerWho was studied is listed further down the page.
Which registered measures put each goal on this table
Cholesterol
low density lipoprotein cholesterol; total cholesterol; non high density lipoprotein cholesterol
Sorted by fixed word lists, version v1. A name the rules do not recognise stays unsorted rather than moving to the nearest column.
What each mark on this table means
∅ Nothing in the sources checked
No registered study lists a life outcome for this goal.
△ Only a number moved
3 registered test measure.
— Not recorded
Harms were not a registered measure for this goal.
… Waiting for a reviewer
Who was studied is listed further down the page.
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.
Percentage change in LDL cholesterol from baseline to week 26
✓ The study showed what it set out to show
Who was studied
Mipomersen HoFH phase 3 (NCT00607373)
How many people
51
Study design
Phase 3
Compared against
Not recorded for this study
Kind of result
A number that stands in for health
What was found
p=0.0003
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. Alanine aminotransferase at least 3x upper limit of normal in 12 percent of treated patients and none on placebo; four discontinuations for adverse events, all in the mipomersen arm; hepatic fat accumulation measured only in the companion HeFH and hyperlipidaemia trials
How far it carries. This study is recorded from the curated record, not from the registry match.
Form and route. Subcutaneous injection of an unconjugated full-phosphorothioate 2-prime-MOE gapmer
Interval reported. Not recorded in this summary
Written into the record, not signed off as a reviewed claim.
KYNAMRO (mipomersen sodium) US prescribing information, 2013 (https://www.accessdata.fda.gov/drugsatfda_docs/label/2013/203568s000lbl.pdf) · a recorded source, not a stored snapshot
Kynamro refusal of marketing authorisation, European Medicines Agency (https://www.ema.europa.eu/en/medicines/human/EPAR/kynamro) · a recorded source, not a stored snapshot
RNAWiki holds 1 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 happened in people◇Read from sources, not yet reviewed
How close this is to real life
The top step is something a person would feel or care about. The bottom is a guess from software. Filled steps are where evidence exists for this substance.
□Living longer, or avoiding a major eventNo evidence recorded. Death, a heart attack, a stroke, a hospital stay.No registered study measures this.
□What a body can do day to dayNo evidence recorded. Walking, dressing, breathing, recovering.No registered study measures this.
□Measured performanceNo evidence recorded. How much was lifted, how far was run, how fast.No registered study measures this.
□Symptoms and quality of lifeNo evidence recorded. Pain, tiredness, mood, sleep, as the person rated it.No registered study measures this.
■A number that stands in for healthEvidence recorded. Cholesterol, blood sugar, bone density. A stand-in, not the thing itself.5 registered measures of this kind.
■A step measured inside a personEvidence recorded. Something measured in human tissue or human cells.A human record sits on the stored organism ladder.
□AnimalsNo evidence recorded. Mice, rats, dogs. Useful for ideas, not proof about people.No animal record is stored.
□Cells in a dishNo evidence recorded. Cells or chemistry on a bench, far from a whole body.No cell or bench record is stored.
□A guess from softwareNo evidence recorded. Nobody measured it. RNAWiki never publishes one as a finding.RNAWiki stores no prediction for this record. Software can suggest a link. RNAWiki does not publish one as a finding.
Higher on these steps means closer to something a person would feel. It does not mean better done.
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
Mipomersen
What a person takes: Subcutaneous injection of an unconjugated full-phosphorothioate 2-prime-MOE gapmer.
The measurement behind this step
Single-use vials or prefilled syringes delivering 200 mg weekly, distributed only through a restricted REMS programme because of hepatotoxicity risk. No targeting ligand of any kind.
Getting in
Weekly subcutaneous injection
A weekly injection under the skin, which caused a local reaction in most patients.
──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
Unconjugated full-phosphorothioate 20-mer, 200 mg weekly. Injection-site reactions occurred in 84 percent of patients, a direct consequence of high local phosphorothioate concentration.
KYNAMRO (mipomersen sodium) US prescribing information, 2013 (https://www.accessdata.fda.gov/drugsatfda_docs/label/2013/203568s000lbl.pdf) · a recorded source, not a stored snapshot
Kynamro refusal of marketing authorisation, European Medicines Agency (https://www.ema.europa.eu/en/medicines/human/EPAR/kynamro) · a recorded source, not a stored snapshot
Reaching the cell
Uptake into hepatocytes without a targeting ligand
Liver cells take the strand in on their own, but so do kidney and immune cells, because nothing directs it.
╌╌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
Phosphorothioate-driven adsorptive endocytosis. Without a GalNAc ligand, hepatocyte delivery is a matter of pharmacokinetic preference rather than targeting, which is why the required dose was high.
KYNAMRO (mipomersen sodium) US prescribing information, 2013 (https://www.accessdata.fda.gov/drugsatfda_docs/label/2013/203568s000lbl.pdf) · a recorded source, not a stored snapshot
Kynamro refusal of marketing authorisation, European Medicines Agency (https://www.ema.europa.eu/en/medicines/human/EPAR/kynamro) · a recorded source, not a stored snapshot
What it acts on
Hybridising to apoB-100 messenger RNA
It pairs with the instructions for the scaffolding protein of every LDL particle.
╌╌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
Watson-Crick binding within the apoB coding region at positions 3249 to 3268. The label records that the effect was shown to be highly sequence-specific in hepatoma cells and primary hepatocytes.
KYNAMRO (mipomersen sodium) US prescribing information, 2013 (https://www.accessdata.fda.gov/drugsatfda_docs/label/2013/203568s000lbl.pdf) · a recorded source, not a stored snapshot
Kynamro refusal of marketing authorisation, European Medicines Agency (https://www.ema.europa.eu/en/medicines/human/EPAR/kynamro) · a recorded source, not a stored snapshot
The change it makes
RNase H destroys the transcript
A cellular enzyme cuts up the paired instructions so the protein is never translated.
╌╌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
RNase H-mediated degradation of the apoB mRNA at the deoxynucleotide gap, inhibiting translation of apoB-100 and therefore assembly of VLDL, the metabolic precursor of LDL.
KYNAMRO (mipomersen sodium) US prescribing information, 2013 (https://www.accessdata.fda.gov/drugsatfda_docs/label/2013/203568s000lbl.pdf) · a recorded source, not a stored snapshot
Kynamro refusal of marketing authorisation, European Medicines Agency (https://www.ema.europa.eu/en/medicines/human/EPAR/kynamro) · a recorded source, not a stored snapshot
What that does for a person
LDL falls, and triglyceride accumulates in the liver
Fewer cholesterol particles circulate, because the liver can no longer package fat for export. The fat stays behind.
──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
Reduced VLDL secretion lowers plasma LDL by about a quarter. The triglyceride that would have been exported accumulates as hepatic steatosis, measured as a median 10 percentage point absolute increase in liver fat at 26 weeks. The therapeutic effect and the toxicity are two readings of the same event.
KYNAMRO (mipomersen sodium) US prescribing information, 2013 (https://www.accessdata.fda.gov/drugsatfda_docs/label/2013/203568s000lbl.pdf) · a recorded source, not a stored snapshot
Kynamro refusal of marketing authorisation, European Medicines Agency (https://www.ema.europa.eu/en/medicines/human/EPAR/kynamro) · 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 it would be like to take◇Read from sources, not yet reviewed
Felt, measured, or meaningful
Three different things that get called the same word. Registered studies measured all three, and mixing them is how a blood test becomes a health claim.
Felt
Things a person could notice without a test.
No registered study measured anything of this kind.
Measured
Things only a test, a scale or a device shows.
low density lipoprotein cholesterol
total cholesterol
non high density lipoprotein cholesterol
maximum plasma concentration
time to maximal concentration
Meaningful
Things that change how a life goes, not only a number.
No registered study measured anything of this kind.
A registered study says what someone planned to measure. It does not say what they found. A number moving is not the same as a life going better. The two are shown apart here.
Felt, but not shown to help. A person notices a change. No study showed it leads anywhere good.
Measured, but not felt. A number moves. The person notices nothing. Both can be true.
Measured, but not shown to matter. A number moves in the good direction. Nobody showed that lives went better.
Matters, but takes years. The result that counts may take longer than anyone would keep watching.
Names that fit none of the three (3)
summary of adverse events
qtcf
area under the curve
These are harms, study-process measures, or names the rules did not recognise. They are shown rather than dropped.
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.
It was used in adults with HoFH on maximally tolerated lipid-lowering therapy. It is no longer marketed anywhere and the US approval has been withdrawn.
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.
Where the result stopped carrying
Hepatic steatosis proved to be a consequence of the mechanism, not a manageable side effect
The EMA refused authorisation in December 2012 and confirmed the refusal in March 2013
Sales were discontinued on 31 May 2018 and the US approval was withdrawn in 2019
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 for a different goal
The studies measured something else entirely.
On this record: Some registered studies measured things that match no goal on this page.
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 (10)
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
Varies by country
❝ 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
Subcutaneous injection of an unconjugated full-phosphorothioate 2-prime-MOE gapmer
✎ 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.
A register records the withdrawal of an approval.
No source is stored against this line.
What is in the pack
Single-use vials or prefilled syringes delivering 200 mg weekly, distributed only through a restricted REMS programme because of hepatotoxicity risk. No targeting ligand of any kind.
✎ 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 hepatotoxicity, with transaminase and bilirubin monitoring before and during treatment and mandatory dose interruption at three times the upper limit of normal. Injection-site reactions in 84 percent, flu-like symptoms in 30 percent, nausea and headache common.
Nobody counted how many people took this and were fine, so this cannot be turned into a rate.
Where this came from
KYNAMRO (mipomersen sodium) US prescribing information, 2013 (https://www.accessdata.fda.gov/drugsatfda_docs/label/2013/203568s000lbl.pdf) · a recorded source, not a stored snapshot
Kynamro refusal of marketing authorisation, European Medicines Agency (https://www.ema.europa.eu/en/medicines/human/EPAR/kynamro) · 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∅Nothing found in the sources checked
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
Subcutaneous injection of an unconjugated full-phosphorothioate 2-prime-MOE gapmer
✎ 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
No targeting ligand of any kind.
✎ 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.
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, withdrawn medicine. The questions below are for a clinician or pharmacist.
Questions worth asking
Which of the trials of Mipomersen 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 LDL reduction translates into fewer cardiovascular events; no outcome trial was ever run
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 LDL surrogate transfers across mechanisms, when the mechanism here traps lipid in the liver
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 fast does the body clear it?
The sources RNAWiki checked hold nothing for this field.
Why it matters. Without this, nothing on this page can say how long anything lasts.
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 Mipomersen 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.
LDL cholesterol fell 24.7 percent against 3.3 percent on placebo
In plain words
In 51 patients with the most severe inherited cholesterol disorder, treated patients dropped their LDL by about a quarter over 26 weeks.
What was measured
LDL cholesterol -24.7 percent versus -3.3 percent, p=0.0003
Effect estimate
No reviewed effect estimate exists for this record.
Limits
See the technical detail.
From the source
NCT00607373 randomised 34 patients to mipomersen and 17 to placebo on top of maximally tolerated lipid-lowering therapy. Mean percentage change in LDL cholesterol was -24.7 percent (95 percent CI -31.6 to -17.7) with mipomersen against -3.3 percent (95 percent CI -12.1 to 5.5) with placebo, p=0.0003. The FDA label reports the same trial as -25 percent mean and -19 percent median, with a treatment difference against placebo of -21 percent.
Written into the record, not signed off as a reviewed claim
Hepatic fat rose by a median of 10 percentage points in 26 weeks
In plain words
Blocking the export of fat from the liver left the fat in the liver. On MRI, liver fat went from zero to about ten percent in half a year.
What was measured
Median absolute hepatic fat increase 10 percentage points at 26 weeks; ALT at least 3x ULN in 12 percent
Effect estimate
No reviewed effect estimate exists for this record.
Limits
This entry records a failure.
From the source
The boxed warning records a median absolute increase in hepatic fat of 10 percent after 26 weeks of treatment, from 0 percent at baseline, measured by magnetic resonance imaging, in the heterozygous FH and hyperlipidaemia trials. Alanine aminotransferase rose to at least three times the upper limit of normal in 4 of 34 treated HoFH patients (12 percent) against none on placebo. Hepatic steatosis is a risk factor for steatohepatitis and cirrhosis, and the long-term consequence was never established.
Source
KYNAMRO US prescribing information, boxed warning
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
LDL lowering was treated as cardiovascular benefit, which was never tested
In plain words
No trial ever asked whether mipomersen prevented heart attacks. The approval rested entirely on the cholesterol number.
What was measured
That a 25 percent LDL reduction achieved by blocking apoB synthesis reduces cardiovascular events
Effect estimate
No reviewed effect estimate exists for this record.
Limits
See the technical detail.
From the source
The pivotal trial was 26 weeks long with a lipid primary endpoint in 51 patients. No cardiovascular outcome trial was conducted before or after approval. LDL reduction is one of the best-supported surrogates in medicine, but that support comes from trials of drugs that lower LDL by increasing receptor-mediated clearance, not by trapping lipid in the liver. The mechanism matters to whether the surrogate transfers.
Written into the record, not signed off as a reviewed claim
The European Medicines Agency refused authorisation, twice
In plain words
European regulators looked at the same data in 2012 and said the risks outweighed the benefit. They said the same again on re-examination in 2013.
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 CHMP adopted a negative opinion on 13 December 2012 and confirmed the refusal on re-examination on 21 March 2013. Mipomersen was therefore approved in the United States and never authorised in the European Union, one of two drugs in this file where the two regulators diverged on the same dossier.
Source
European Medicines Agency, Kynamro refusal of marketing authorisation
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
Sales stopped in 2018 and the approval was withdrawn in 2019
In plain words
The drug passed through three owners, never sold, was pulled from the market in May 2018, and the FDA formally withdrew its approval the following year.
What was measured
Injection-site reactions in 84 percent and flu-like symptoms in 30 percent of patients
Effect estimate
No reviewed effect estimate exists for this record.
Limits
This entry records a failure.
From the source
Kynamro moved from Genzyme back to Ionis and then to Kastle Therapeutics. Sales were discontinued on 31 May 2018 and the new drug application was among those withdrawn by the FDA in 2019. Restricted distribution under a REMS, weekly injection-site reactions in 84 percent of patients and flu-like symptoms in 30 percent left it with almost no prescribing base once lomitapide and later evinacumab arrived.
Source
FDA Federal Register notice, Withdrawal of Approval of 11 New Drug Applications, 2019; KYNAMRO label sections 5.3 and 5.4
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 field moved from blocking assembly to a receptor-independent antibody
In plain words
Both drugs that stopped the liver exporting fat caused fatty liver. The lasting answer for this disease came from a different mechanism entirely.
What was measured
Not recorded
Effect estimate
No reviewed effect estimate exists for this record.
Limits
See the technical detail.
From the source
Mipomersen and lomitapide both block lipoprotein assembly and both cause hepatic steatosis, which now looks like a mechanistic consequence rather than an accident of either molecule. Evinacumab, an ANGPTL3 antibody, lowered LDL by about half in a randomised placebo-controlled HoFH trial without that trade-off. The apoB antisense idea itself has not returned in this indication.
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What is not here
4 questions this page could not answer
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The record as stored
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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.
An antisense drug that lowered LDL cholesterol by 25 percent in 34 patients with homozygous familial hypercholesterolaemia by shutting down apolipoprotein B production, was refused by European regulators for hepatic steatosis, and had its US approval withdrawn in 2019 after sales ceased.
Recorded evidence blocks (7)
Q1
What did Mipomersen's largest trial (309 people) and its longest (6.4 years) measure?
309 people in Mipomersen's largest registered study, 6.4 years in its longest registered window, measuring Maximum plasma concentration (Cmax). ClinicalTrials.gov · 2026-09-01
7 phase3, 4 phase1, 4 phase2; NCT00694109; 2014-09; no ageing endpoint recorded. Last human test completed 2015, NCT01475825.
Interpretation These counts include studies where Mipomersen was a comparison treatment, a background treatment or an exposure in an observational study, and the longest window may be a planned end date. Trial roles have not yet been classified for this record.
Show the evidence
phase3
7
phase1
4
phase2
4
Last recorded human testNCT01475825
2015-12-29
recorded 2026-09-01 · last checked 2026-09-04
Q2
Mipomersen was tested only in human — what did it show?
2 recorded entries; human; also "mipomersen sodium 70 mg"
Show the evidence
human
NCT01475825
mipomersen sodium 200 mg
NCT01475825
mipomersen sodium 70 mg
recorded 2026-09-01 · last checked 2026-09-04
Q4
Could one person measure Mipomersen's effect on low density lipoprotein cholesterol?
Low density lipoprotein cholesterol: measured in Mipomersen's trials.
Interpretation low density lipoprotein cholesterol is the recorded endpoint.
Show the evidence
biomarkers
low density lipoprotein cholesterol; 2026-09-01
total cholesterol; 2026-09-01
non high density lipoprotein cholesterol; 2026-09-01
summary of adverse events; 2026-09-01
maximum plasma concentration; 2026-09-01
time to maximal concentration; 2026-09-01
2 more recorded rows
biomarkers
qtcf; 2026-09-01
biomarkers
area under the curve; 2026-09-01
human trials at or under30
5
Not recorded for this substance
a recorded half-life
smallest human trial
12; NCT00280995; PHASE2; the smallest recorded human enrolment at or below 30; the registry states no direction of its result; COMPLETED
Q5
Which of area under the curve, low density lipoprotein cholesterol and maximum plasma concentration did Mipomersen's trials measure?
area under the curve, low density lipoprotein cholesterol and maximum plasma concentration lead 8 outcome terms across Mipomersen's trials. ClinicalTrials.gov · 2026-09-01
Interpretation summary of adverse events, maximum plasma concentration, time to maximal concentration, qtcf and area under the curve follow.
Show the evidence
low density lipoprotein cholesterol
1
total cholesterol
1
non high density lipoprotein cholesterol
1
summary of adverse events
1
maximum plasma concentration
1
time to maximal concentration
1
2 more recorded rows
qtcf
1
area under the curve
1
recorded 2026-09-01 · last checked 2026-09-04
Q6
Which 6 trials of Mipomersen posted no result?
Posted no result
6 of 6 completed trials
Registrations
NCT00280995, NCT01090661, NCT01061814, NCT01299298, NCT01414881 and NCT01598948
Completion dates
oldest 2007-08; newest 2015-06
Show the evidence
Trial
NCT00280995
2007-08
NCT01090661
2010-05
NCT01061814
2010-06
NCT01299298
2011-04
NCT01414881
2012-11
NCT01598948
2015-06
Q7
At the median, Mipomersen's trials enrolled 51 people — anything larger?
Median enrolment
51
Largest enrolment
309
Registered trials counted
15
Where it is registeredIdentifiers, relations and other names
ChEMBL ATC CC BY-SA · ClinicalTrials.gov — US Government work · Europe PMC — metadata only, under the recorded legal gate · derived from this page's own recorded fields; no external licence · mixed register set; per-register licences in docs/specs/corpus-20k-sources.md
✗ required summary fields resolved: 4 required field(s) not terminal: Why people use it, Best-supported result, Biggest unanswered question, Human evidence
✓ public claims reviewed: 0 reviewed claim(s); drafts are never rendered
✓ source coverage passed: 5 source rows
✓ no critical contamination: no quarantine open
✓ canonical metadata passed: slug and display name present
✓ no raw internal fields: enforced by the copy-contract test over the rendered page
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