This page shows what was measured, who it was measured in, and what that does not settle.
What Inclisiran does in the body
Used with diet and exercise to lower LDL, often called “bad” cholesterol.
Your liver pulls cholesterol out of the blood using catchers on its surface called LDL receptors. A protein named PCSK9 grabs those catchers and drags them off to be destroyed, so you end up with fewer of them. Inclisiran is a short piece of RNA with a sugar tag that only liver cells recognise; once inside, it hands the liver a template for shredding its own PCSK9 instructions. The catchers survive and get reused, and LDL in the blood falls for about six months per injection.
What happened in people
After about 17 months, two large studies found that LDL fell by about half on average compared with look-alike injections containing no inclisiran.
✓ 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
Completed studies have not yet shown whether inclisiran prevents heart attacks or strokes.
Where it acts
Hepatocyte cytoplasm (liver)
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.
Where each sentence above came from
The recorded explanation is written in label language rather than for a beginner. 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 123 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.
Messenger RNA
Messenger RNA is a working copy of one gene, carried to where proteins are built.
A picture of it, and where the picture fails
It is like a photocopy of one plan page, taken to the workshop.
Where that stops being true. A photocopy lasts. This copy is destroyed soon after use, on purpose.
What people get wrong. It is often thought to change the gene. It is a copy, and it does not alter the original.
A single-stranded transcript of a gene that ribosomes translate into a protein.
Small interfering RNA
A small interfering RNA is a short piece that makes a cell destroy one working copy.
A picture of it, and where the picture fails
It is like a note telling the workshop to shred one plan page.
Where that stops being true. A note is read once. This keeps working for months after one injection.
What people get wrong. It is often described as gene editing. It leaves the gene untouched.
A short double-stranded RNA that directs the RNA-induced silencing complex to cleave a complementary transcript.
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 27 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 moved9 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
ldl c from baseline to day 510; low density lipoprotein cholesterol from baseline to day 150; ldl c from baseline to day 330; ldl c; ldl c change; ldl c from baseline; low density lipoprotein cholesterol; ldl c level
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
9 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.
Results from the one trial this record names
In NCT03399370, Percentage Change in LDL-C From Baseline to Day 510 (least squares mean) was -56.34 percent change (95% CI -58.35 to -54.34), inclisiran group against 1.30 percent change, placebo group in the comparison group at Baseline, Day 510. (p value <.0001 (superiority, LS mean difference from placebo))
ClinicalTrials.gov record · NCT03399370 · read 2026-08-27
Percentage change in LDL-C from baseline to day 510 in heterozygous FH
✓ The study showed what it set out to show
Who was studied
ORION-9 (NCT03397121)
How many people
482
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 < 0.001
Repeated elsewhere
Replicated
What this does not prove. Meeting one endpoint in one population does not carry to other goals or other people.
The limits of this study, and where it came from
Main limit. No limitation is recorded for this study.
How far it carries. This study is recorded from the curated record, not from the registry match.
Form and route. GalNAc-conjugated siRNA, subcutaneous prefilled syringe
Interval reported. Not recorded in this summary
Written into the record, not signed off as a reviewed claim.
RNAWiki holds 6 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 eventEvidence recorded. Death, a heart attack, a stroke, a hospital stay.1 registered measure of this kind. No reviewed result.
□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.10 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.
Where a source records it acting
Liver: High uptake into, and selectivity for, the liver — the target organ for cholesterol lowering, as recorded
US prescribing information · 6fc0afca-4513-4c35-b594-6544aee29a44 · read 2026-08-27
Start
Inclisiran
What a person takes: GalNAc-conjugated siRNA, subcutaneous prefilled syringe.
The measurement behind this step
A single-dose prefilled syringe containing 284 mg of inclisiran in 1.5 mL, given by a healthcare professional at day 1, month 3, and every 6 months thereafter. No lipid nanoparticle and no premedication: the triantennary GalNAc ligand does the targeting on its own.
Getting in
Subcutaneous dose, then a sugar tag finds the liver
The injection goes under the skin. Three sugar molecules on the end of the drug act as a postcode that only liver cells read, so almost all of it ends up where it is meant to be.
╌╌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 triantennary N-acetylgalactosamine ligand (L96) is attached to the 3' terminus of the 21-mer sense strand and binds the asialoglycoprotein receptor, which is expressed at roughly a million copies per hepatocyte and recycles every 15 minutes.
The liver cell swallows the drug in a bubble. Most of it is broken down, but a small fraction leaks into the cell body and is held there for months, which is why one injection lasts half a year.
──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
Clathrin-mediated endocytosis delivers the duplex to the endosome. A small proportion escapes into the cytoplasm; the rest forms a slowly released intracellular depot, which is what decouples the plasma half-life of hours from the pharmacodynamic duration of months.
The guide strand is loaded into the cell's own cutting machine
The two strands separate. One is discarded; the other is loaded into a protein complex the cell already uses to silence its own genes.
╌╌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 23-nucleotide antisense strand is loaded into Argonaute 2 within the RNA-induced silencing complex. The sense strand is cleaved and discarded. The 2'-F and 2'-OMe ribose modifications and the six terminal phosphorothioate linkages are what let the strand survive nuclease attack long enough to be loaded.
PCSK9 messenger RNA is cut, and the complex moves on
The loaded complex hunts down the instructions for PCSK9 and cuts them. It then releases the pieces and goes looking for the next copy, which is why so little drug does so much.
╌╌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 strand base-pairs with a conserved site in the 3' untranslated region of PCSK9 mRNA with full complementarity, and Argonaute 2 catalyses endonucleolytic cleavage between the nucleotides paired to guide positions 10 and 11. The cleaved transcript is degraded by cellular exonucleases and the complex is recycled — a catalytic, not stoichiometric, mechanism.
With less PCSK9 around, the liver keeps its cholesterol catchers instead of destroying them. More catchers means more LDL cleared from the blood.
╌╌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
Reduced PCSK9 secretion means fewer LDL receptors are routed to lysosomal degradation after endocytosis, so surface receptor density rises and hepatic LDL particle clearance increases. In ORION-10 and ORION-11 this produced a 52.3% and 49.9% placebo-adjusted LDL-C reduction at day 510.
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.
ldl c from baseline to day 510
low density lipoprotein cholesterol from baseline to day 150
ldl c from baseline to day 330
ldl c
ldl c change
ldl c from baseline
low density lipoprotein cholesterol
ldl c level
blood pressure
ldl c levels
Meaningful
Things that change how a life goes, not only a number.
major adverse cardiovascular event
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 (16)
incidence of treatment emergent adverse events
carotid 68ga dotatate pet
carotid upsa imaging
cardiovascular events
treatment emergent adverse events and serious adverse events
adverse events
plaque quantification
quantification of stenosis
quantification of pericoronary fat attenuation
quantification of epicardial fat attenuation
atheroma volume
incidence and type of treatment emergent adverse events
lipid profile
cimt
incidences of adverse events/adverse drug reactions
lp 125
These are harms, study-process measures, or names the rules did not recognise. They are shown rather than dropped.
What it would be like to take◇Read from sources, not yet reviewed
How long anything takes
Nine different lengths of time that get confused with each other. None of them is worked out from another.
Before anything is noticed.RNAWiki does not store this separately, and never works it out from another figure on this page.
Before a test result moves.RNAWiki does not store this separately, and never works it out from another figure on this page.
Before performance moves.RNAWiki does not store this separately, and never works it out from another figure on this page.
How long the result was watched.No finished study window is recorded for a study that tested this substance.
How long people took it.How long people actually took it is not stored. The study window is not the same thing.
How long people were followed.Follow-up length is not stored separately. It is never read off the study window, which would be a different thing.
How fast the body clears it. approximately 9 hours hours
Read from the label, which states: “The terminal elimination half-life of LEQVIO is approximately 9 hours, and no accumulation occurs with multiple dosing.”
How long effects linger.RNAWiki does not store this separately, and never works it out from another figure on this page.
Beyond the studies. Nothing is recorded about the long term.
The longest finished study sets the edge of what anyone measured.
A study window is not how long people took it, and neither is how long they were followed. Where RNAWiki holds only one of the three, it shows one.
What is missing or unclear◇Read from sources, not yet reviewed
Were people like you studied?
RNAWiki cannot tell whether a study fits you. It can show who was in it, and where the result stops carrying.
Who was studied
People similar to this profile were included.
Adults with hypercholesterolemia or heterozygous familial hypercholesterolemia who are already on the highest statin dose they tolerate, and patients aged 12 and older with familial hypercholesterolemia.
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.
Who a named study recorded including and excluding
It included: Male or female participants ≥18 years of age.; History of ASCVD (coronary heart disease [CHD], cardiovascular disease [CVD], or peripheral arterial disease [PAD]).; Serum LDL-C ≥1.8 millimole (mmol)/liter (L) (≥70 mg/dL).; Fasting triglyceride <4.52 mmol/L (<400 mg/dL) at screening.; Participants on statins should be receiving a maximally tolerated dose.; Participants not receiving statins must have documented evidence of intolerance to all doses of at least 2 different statins..
ClinicalTrials.gov record · NCT03399370 · read 2026-08-27
It excluded: New York Heart Association (NYHA) class IV heart failure.; Uncontrolled cardiac arrhythmia; Uncontrolled severe hypertension; Active liver disease; Treatment with other investigational products or devices within 30 days or 5 half-lives of the screening visit, whichever is longer.; Treatment (within 90 days of screening) with monoclonal antibodies directed towards PCSK9.
ClinicalTrials.gov record · NCT03399370 · read 2026-08-27
What the label states about particular groups
On pediatric, the label states: “The safety and effectiveness of LEQVIO have not been established in pediatric patients with HeFH or HoFH younger than 12 years of age.”
US prescribing information · 6fc0afca-4513-4c35-b594-6544aee29a44 · read 2026-08-30
On older people, the label states: “Of the 1,833 patients treated with LEQVIO in clinical trials, 981 (54%) patients were 65 years of age and older, while 239 (13%) patients were 75 years of age and older.”
US prescribing information · 6fc0afca-4513-4c35-b594-6544aee29a44 · read 2026-08-30
On people who are pregnant, the label states: “Risk Summary Discontinue LEQVIO when pregnancy is recognized.”
US prescribing information · 6fc0afca-4513-4c35-b594-6544aee29a44 · read 2026-08-30
On people who are breastfeeding, the label states: “Risk Summary There is no information on the presence of inclisiran in human milk, the effects on the breastfed infant, or the effects on milk production.”
US prescribing information · 6fc0afca-4513-4c35-b594-6544aee29a44 · read 2026-08-30
On people with reduced liver function, the label states: “No dose adjustment is necessary in patients with mild to moderate hepatic impairment.”
US prescribing information · 6fc0afca-4513-4c35-b594-6544aee29a44 · read 2026-08-30
On people with reduced kidney function, the label states: “No dose adjustments are necessary for patients with mild, moderate, or severe renal impairment [see Clinical Pharmacology (12.3)] .”
US prescribing information · 6fc0afca-4513-4c35-b594-6544aee29a44 · read 2026-08-30
Where the result stopped carrying
ORION-5: no LDL-C change in adults with homozygous familial hypercholesterolemia despite a 60.6% PCSK9 reduction
The December 2020 FDA complete response letter, caused by an uninspected third-party manufacturing site rather than by the data
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
Given by a clinician
❝ Quoted from a source
Where this came from
Copied from a source RNAWiki stored, with the source named.
A person wrote this into the record with the study named beside it. No reviewer has signed it off.
The form and route recorded on this substance.
No source is stored against this line.
Who oversees it
Professional supervision is normally required. It is a prescription or clinician-administered medicine where it is approved.
❝ Quoted from a source
Where this came from
Copied from a source RNAWiki stored, with the source named.
The identity record classes it as siRNA (Small Interfering RNA).
No source is stored against this line.
What is in the pack
5 mL, given by a healthcare professional at day 1, month 3, and every 6 months thereafter. No lipid nanoparticle and no premedication: the triantennary GalNAc ligand does the targeting on its own.
✎ 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
The FDA label carries one warning, hypersensitivity reactions including anaphylaxis and angioedema, and contraindicates the drug after a prior serious reaction. Adverse reactions at 3% or more in trials were injection-site reaction, arthralgia and bronchitis. No hepatic or renal toxicity signal was identified in the phase 3 programme.
Nobody counted how many people took this and were fine, so this cannot be turned into a rate.
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.
Inclisiran appears in spontaneous reports to regulators. Across the 10 most-reported reaction terms, 35 reaction mentions were counted. One report can name several reactions.
open-targets-adr · recorded 2026-06-24 · 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.
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
thcare professional at day 1, month 3, and every 6 months thereafter. No lipid nanoparticle and no premedication: the triantennary GalNAc ligand does the targeting on its own.
✎ 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
5 products list this as an active ingredient in the United States drug directory. 5 of them contain it and nothing else.
FDA National Drug Code directory · 0078-1000 · read 2026-08-29
They are sold as injection, solution, liquid and powder, taken subcutaneous.
FDA National Drug Code directory · 0078-1000 · 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 · 6fc0afca-4513-4c35-b594-6544aee29a44 · read 2026-08-29
Those labels are classed as human prescription drug.
US prescribing information · 6fc0afca-4513-4c35-b594-6544aee29a44 · read 2026-08-29
LEQVIO is injection, single-dose prefilled syringe at 284 mg/1.5 mL (189 mg/mL), recorded as prescription product; fda label in effect 2026-08-19 in the United States.
US prescribing information · 6fc0afca-4513-4c35-b594-6544aee29a44 · read 2026-08-27
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 Inclisiran 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 inclisiran reduces heart attacks, strokes or cardiovascular death — no completed trial has measured this
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 two injections a year is equivalent to a daily statin on outcomes, when only one of the two has outcome data
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 exploratory pooled MACE signal (OR 0.74) is an outcome result; it is a post-hoc analysis of trials designed and powered for a lipid 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.
What is missing or unclear◇Read from sources, not yet reviewed
What nobody knows yet
Open questions, each with why it is open and what would close it.
Missing populations
Which groups were under-represented in the studies has not been recorded.
Why it matters. Recorded by the evidence model as a gap on this record.
What would answer it
A study that measures it, and a reviewer to sign it off.
Last checked 2026-09-04. Searched: The sources listed in the receipts at the foot of this page.
Missing long-term data
No completed tested study window is recorded.
Why it matters. Recorded by the evidence model as a gap on this record.
What would answer it
A study that measures it, and a reviewer to sign it off.
Last checked 2026-09-04. Searched: The sources listed in the receipts at the foot of this page.
No reviewed conclusion
RNAWiki has not yet published a reviewed conclusion for this use.
Why it matters. Recorded by the evidence model as a gap on this record.
What would answer it
A study that measures it, and a reviewer to sign it off.
Last checked 2026-09-04. Searched: The sources listed in the receipts at the foot of this page.
Missing interaction studies
No interaction was found in the registers checked. Not finding one is not the same as showing there is none.
Why it matters. Recorded by the evidence model as a gap on this record.
What would answer it
A study that measures it, and a reviewer to sign it off.
Last checked 2026-09-04. Searched: The sources listed in the receipts at the foot of this page.
Formulation uncertainty
Several salts, forms or products of Inclisiran 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.
ORION-10 and ORION-11: 52.3% and 49.9% placebo-adjusted LDL-C reduction at day 510
In plain words
Two trials, 3,178 patients between them, both showed LDL cholesterol about half of what the placebo group reached, held there for 17 months on two injections a year.
What was measured
Percentage change in serum LDL-C at day 510 versus placebo
Effect estimate
No reviewed effect estimate exists for this record.
Limits
See the technical detail.
From the source
Randomised, double-blind, placebo-controlled. Baseline LDL-C 104.7 mg/dL (ORION-10, n=1561) and 105.5 mg/dL (ORION-11, n=1617). Day-510 reduction 52.3% (95% CI 48.8 to 55.7) and 49.9% (95% CI 46.6 to 53.1); time-adjusted reductions 53.8% and 49.2%; P<0.001 for all comparisons against placebo.
Written into the record, not signed off as a reviewed claim
Cardiovascular benefit is inferred from LDL biology, not measured for this drug
In plain words
No completed trial has shown that inclisiran prevents heart attacks or strokes. The argument that it does is borrowed from statins, where lowering LDL did reduce events.
What was measured
That a 50% LDL-C reduction with inclisiran translates into the event reduction seen with statins and PCSK9 antibodies
Effect estimate
No reviewed effect estimate exists for this record.
Limits
See the technical detail.
From the source
ORION-4 (NCT03705234, 16,124 participants) is active but not recruiting with a primary completion date of October 2026, and VICTORION-2-PREVENT (NCT05030428, 17,004 participants) runs to October 2027. Neither has reported. The only cardiovascular signal is a post-hoc patient-level pooling of the phase 3 lipid trials, in which composite MACE fell (OR 0.74, 95% CI 0.58 to 0.94) while the individual components did not reach significance: myocardial infarction OR 0.80 (0.50 to 1.27) and stroke OR 0.86 (0.41 to 1.81). Drug and Therapeutics Bulletin reviewed that analysis under the headline "No meaningful cardiovascular outcome data for inclisiran".
Written into the record, not signed off as a reviewed claim
ORION-5: no LDL-C reduction in adults with homozygous familial hypercholesterolemia
In plain words
In the most severe inherited form of high cholesterol, inclisiran wiped out PCSK9 exactly as designed and LDL cholesterol did not move.
What was measured
Placebo-corrected percentage change in LDL-C at day 150
Effect estimate
No reviewed effect estimate exists for this record.
Limits
This entry records a failure.
From the source
Phase 3, 56 patients, randomised 2:1. Placebo-corrected change in LDL-C from baseline to day 150 was -1.68% (95% CI -29.19 to 25.83; P=0.90), while PCSK9 fell 60.6% (P<0.0001). Apolipoprotein B, total cholesterol and non-HDL-C were likewise unchanged. The mechanism needs a working LDL receptor to act on, and in HoFH there is little or none.
Written into the record, not signed off as a reviewed claim
Adolescent HoFH was later approved on 13 patients, after the adult HoFH trial failed
In plain words
The adult trial in homozygous familial hypercholesterolemia found nothing. A 13-patient adolescent trial found a 33% reduction, and the label now covers 12-year-olds with the same condition.
What was measured
Not recorded
Effect estimate
No reviewed effect estimate exists for this record.
Limits
See the technical detail.
From the source
ORION-13 randomised 13 adolescents aged 12 to under 18 with genetically confirmed HoFH, explicitly excluding LDLR null/null genotypes. Placebo-adjusted LDL-C change to day 330 was -33.3% (95% CI -59.2 to -7.3). The exclusion is the whole story: patients with some residual receptor function respond, and the adult ORION-5 population included those with none. The current FDA label carries the pediatric HoFH indication.
Written into the record, not signed off as a reviewed claim
The first FDA submission was refused in December 2020 over a manufacturing inspection
In plain words
The FDA turned inclisiran down a year before approving it, and not because of the science.
What was measured
Not recorded
Effect estimate
No reviewed effect estimate exists for this record.
Limits
This entry records a failure.
From the source
Novartis received a complete response letter on 18 December 2020 citing unresolved facility inspection-related conditions at a third-party manufacturing site that the agency had been unable to inspect during COVID-19 travel restrictions. The letter raised no efficacy or safety concerns. The European Commission had granted marketing authorisation one week earlier, on 11 December 2020; the FDA approved on 22 December 2021.
Source
Novartis media release, 18 December 2020
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
ORION-9: 47.9 percentage-point separation from placebo in heterozygous FH
In plain words
In inherited high cholesterol with one bad copy of the gene, LDL fell 39.7% on inclisiran and rose 8.2% on placebo.
What was measured
Percentage change in LDL-C at day 510 versus placebo
Effect estimate
No reviewed effect estimate exists for this record.
Limits
See the technical detail.
From the source
Phase 3, 482 patients with HeFH, baseline LDL-C 153 mg/dL. Day-510 change was -39.7% (95% CI -43.7 to -35.7) with inclisiran and +8.2% (95% CI 4.3 to 12.2) with placebo, a between-group difference of -47.9 percentage points (95% CI -53.5 to -42.3; P<0.001). Reductions held across FH genotypes.
Written into the record, not signed off as a reviewed claim
ORION-3: LDL-C lowering held for four years of open-label dosing
In plain words
Patients who stayed on inclisiran for four years kept the reduction. The trial was open-label, so this shows durability, not a fresh comparison against placebo.
What was measured
Not recorded
Effect estimate
No reviewed effect estimate exists for this record.
Limits
See the technical detail.
From the source
Four-year open-label extension of the phase 2 ORION-1 trial across 52 sites in five countries (NCT03060577). The inclisiran-only arm continued twice-yearly 300 mg inclisiran sodium; the switching arm received evolocumab to day 360 before transitioning. Endpoints ran to day 1440. No placebo control existed after ORION-1 ended.
This order is fixed in code and does not count clicks or time on the page.
What is not here
3 questions this page could not answer
These sections were prepared and left out because there was nothing to put in them. They are listed rather than hidden, so the gaps in this record are visible.
What it may clash with — found nothing in the sources checked.
Other ways to the same goal — found nothing in the sources checked.
What changed on this page — found nothing in the sources checked.
The record as stored
The full record, for auditing
Everything above is built from what is below. This layer keeps the technical vocabulary, record identifiers and every stored row, so a reader who wants to check the page can.
The older medicine-wide conclusion held in this record
Written for a clinical reader, and about the medicine as a whole rather than about one indication, population and set of trials. RNAWiki does not treat it as a programme conclusion and no reviewer has signed it off in that form. It is here word for word because it is what the record holds.
A GalNAc-tagged siRNA that makes liver cells destroy their own PCSK9 messenger RNA, cutting LDL cholesterol by 52.3% and 49.9% against placebo at day 510 in ORION-10 and ORION-11 — a blood measurement, not yet a demonstrated reduction in heart attacks.
Recorded evidence blocks (12)
Q1
What did Inclisiran's largest trial (204691 people) and its longest (31 years) measure?
204691 people in Inclisiran's largest registered study, 31 years in its longest registered window, measuring Pharmacokinetics: Maximum Observed Plasma Concentration (Cmax) Of Inclisiran. ClinicalTrials.gov · 2026-09-01
24 phase3, 13 phase4, 12 na or unstated, 6 phase2, 4 phase1, 1 na; NCT03705234; 2049-12; no ageing endpoint recorded. Last human test completed 2026, NCT07615166.
Interpretation These counts include studies where Inclisiran 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
24
phase4
13
na or unstated
12
phase2
6
phase1
4
na
1
1 more recorded row
Last recorded human testNCT07615166
2026-06-30
recorded 2026-09-01 · last checked 2026-09-04
Q2
Inclisiran was tested only in human — what did it show?
"study withdrawn, no participants enrolled, changes in the study design planned"; 1 of 60 registered studies
Show the evidence
TrialNCT06280976
withdrawn; "study withdrawn, no participants enrolled, changes in the study design planned"
recorded 2026-09-01 · last checked 2026-09-04
Q4
Human studies of Inclisiran used 100 mg inclisiran sodium (equivalent to 94.5 mg inclisiran) — over how long?
Human studies of Inclisiran used "100 mg inclisiran sodium (equivalent to 94.5 mg inclisiran)". ClinicalTrials.gov · 2026-09-01
5 recorded entries; human; also "300 mg inclisiran sodium (equivalent to 284 mg inclisiran)", "Inclisiran sodium 300 mg", "Inclisiran sodium 300 mg (equivalent to 284 mg inclisiran) in 1.5 mL"
Show the evidence
human
NCT04774003
100 mg inclisiran sodium (equivalent to 94.5 mg inclisiran)
NCT04774003
300 mg inclisiran sodium (equivalent to 284 mg inclisiran)
NCT05030428
Inclisiran sodium 300 mg
NCT05739383
Inclisiran sodium 300 mg (equivalent to 284 mg inclisiran) in 1.5 mL
NCT07421232
Inclisiran (Leqvio®) 300mg
recorded 2026-09-01 · last checked 2026-09-04
Q5
Inclisiran's half-life is approximately 9 hours — which schedules were studied?
approximately 9 hours, the half-life Inclisiran's label states. openfda-label · 6fc0afca-4513-4c35-b594-6544aee29a44 · 2026-08-27
Show the evidence
half life
approximately 9 hours hours; The terminal elimination half-life of LEQVIO is approximately 9 hours, and no accumulation occurs with multiple dosing.
metabolism
Metabolism Inclisiran is primarily metabolized by nucleases to shorter nucleotides of varying length.
recorded 2026-08-27 · last checked 2026-09-04
Q6
Could one person measure Inclisiran's effect on ldl c from baseline to day 510?
Ldl c from baseline to day 510: measured in Inclisiran's trials.
ldl c from baseline to day 510 is the recorded endpoint.
Show the evidence
biomarkers
ldl c from baseline to day 510; 2026-09-01
major adverse cardiovascular event; 2026-09-01
incidence of treatment emergent adverse events; 2026-09-01
low density lipoprotein cholesterol from baseline to day 150; 2026-09-01
carotid 68ga dotatate pet; 2026-09-01
carotid upsa imaging; 2026-09-01
14 more recorded rows
biomarkers
ldl c from baseline to day 330; 2026-09-01
biomarkers
ldl c; 2026-09-01
biomarkers
ldl c change; 2026-09-01
biomarkers
ldl c from baseline; 2026-09-01
biomarkers
cardiovascular events; 2026-09-01
biomarkers
low density lipoprotein cholesterol; 2026-09-01
biomarkers
ldl c level; 2026-09-01
biomarkers
treatment emergent adverse events and serious adverse events; 2026-09-01
biomarkers
adverse events; 2026-09-01
biomarkers
plaque quantification; 2026-09-01
biomarkers
quantification of stenosis; 2026-09-01
biomarkers
quantification of pericoronary fat attenuation; 2026-09-01
biomarkers
quantification of epicardial fat attenuation; 2026-09-01
biomarkers
atheroma volume; 2026-09-01
half life
2026-09-04; halfLife; hours; approximately 9 hours; 2026-08-27
human trials at or under30
4
smallest human trial
0; NCT06280976; PHASE4; the smallest recorded human enrolment at or below 30; the registry states no direction of its result; WITHDRAWN
Q7
Which of adverse events, atheroma volume and blood pressure did Inclisiran's trials measure?
adverse events, atheroma volume and blood pressure lead 27 outcome terms across Inclisiran's trials. ClinicalTrials.gov · 2026-09-01
low density lipoprotein cholesterol from baseline to day 150, carotid 68ga dotatate pet, carotid upsa imaging, ldl c from baseline to day 330, ldl c and ldl c change follow.
Show the evidence
ldl c from baseline to day 510
1
major adverse cardiovascular event
1
incidence of treatment emergent adverse events
1
low density lipoprotein cholesterol from baseline to day 150
1
carotid 68ga dotatate pet
1
carotid upsa imaging
1
14 more recorded rows
ldl c from baseline to day 330
1
ldl c
1
ldl c change
1
ldl c from baseline
1
cardiovascular events
1
low density lipoprotein cholesterol
1
ldl c level
1
treatment emergent adverse events and serious adverse events
1
adverse events
1
plaque quantification
1
quantification of stenosis
1
quantification of pericoronary fat attenuation
1
quantification of epicardial fat attenuation
1
atheroma volume
1
recorded 2026-09-01 · last checked 2026-09-04
Q8
Which of Inclisiran's 29 ongoing trials reports first?
Number of participants with a major adverse cardiovascular event (MACE); Core: Percentage change in low- density lipoprotein cholesterol (LDL-C); latest 2049-12
Show the evidence
Trial
NCT03705234
"A Randomized Trial Assessing the Effects of Inclisiran on Clinical Outcomes Among People With Cardiovascular Disease"; n 16124; "Number of participants with a major adverse cardiovascular event (MACE)"; 2049-12
NCT04765657
"Study of Efficacy and Safety of Inclisiran in Asian Participants With Atherosclerotic Cardiovascular Disease (ASCVD) or ASCVD High Risk and Elevated Low Density Lipoprotein Cholesterol (LDL-C)"; n 345; "Core: Percentage change in low- density lipoprotein cholesterol (LDL-C)"; 2026-12-28
NCT05030428
"Study of Inclisiran to Prevent Cardiovascular (CV) Events in Participants With Established Cardiovascular Disease"; n 17004; "Time to First Occurrence of 3P-MACE (3-Point Major Adverse Cardiovascular Events)"; 2027-05-10
NCT05360446
"Coronary Computed Tomography Study to Assess the Effect of Inclisiran in Addition to Maximally Tolerated Statin Therapy on Atherosclerotic Plaque Progression in Participants With a Diagnosis of Non-obstructive Coronary Artery Disease Without Previous Cardiovascular Events"; n 609; "Percentage change in total coronary atheroma volume"; 2026-10-26
NCT05399992
"Study Evaluating LDL-C Change and Adherence to Inclisiran Lipid-lowering Therapy in ASCVD"; n 847; "Percentage change in LDL-C from baseline to 10 months"; 2026-10-05
NCT05682378
"Long-term Safety and Tolerability of Inclisiran in Participants With HeFH or HoFH Who Have Completed the Pediatric ORION-16, ORION-13, ORION-20, or ORION-19 Studies"; n 195; "Number of participants with treatment-emergent adverse events (TEAEs) and serious adverse events (TESAEs)"; 2032-03-28
14 further recorded trials
NCT05726838
"The Belgian REAL (BE.REAL) Registry"; n 600; "Mean percent change in LDL-C from baseline"; 2029-03-30
NCT05739383
"A Study of Inclisiran to Prevent Cardiovascular Events in High-risk Primary Prevention Patients."; n 14012; "Time to the first occurrence of 4P-MACE"; 2029-04-16
NCT06249165
"VictORION-INCLUSION: Evaluating Inclisiran for Cholesterol Managment in Heart Disease"; n 130; "Achievement of LDL-C targets"; 2027-02-28
NCT06275724
"Specified Drug-use Survey of Leqvio for s.c. Injection."; n 585; "Number of patients with adverse events"; 2026-12-17
NCT06287177
"Multicenter Study on the Evaluation of Adherence, Persistence and Efficacy of Treatment With Inclisiran in Italy"; n 3000; "Description of adherence to treatment with Inclisiran in a real-life Italian population"; 2030-11-01
NCT06338293
"Effects of Inclisiran Combined With Statins on the Morphology of Coronary Vulnerable Plaques"; n 40; "The change rate of the thinnest fibrous cap of vulnerable plaque at the target vascular lesion from baseline to one-year follow-up(△ FCT%)"; 2025-12-31
NCT06372925
"Intravascular Imaging Study of the Effect of Inclisiran on Plaque in Patients With Acute Myocardial Infarction"; n 318; "Change in percent atheroma volume (PAV)"; 2027-01-26
NCT06421363
"Continuity of Care Between Primary Care Cardiology and Specialty Services for Patients With Chronic Ischemic Heart Disease"; n 50; "Change in Unplanned Medical Visits"; 2027-08-01
NCT06494501
"The Prevent Coronary Artery Disease Trial"; n 1600; "Change in atherosclerotic plaque burden from baseline"; 2032-06-30
NCT06501443
"LATAM LOWERS LDL-C"; n 520; "Change in LDL-C from baseline to 330 days"; 2026-11-29
NCT06586684
"Effect of Small Interfering RNA Inclisiran on Carotid Plaques As Assessed by Carotid Ultrasound"; n 40; "CIMT"; 2026-09-30
NCT06597006
"Study to Evaluate Safety, Tolerability and Efficacy of Inclisiran in Children With Homozygous Familial Hypercholesterolemia"; n 9; "Percentage change in LDL-C from baseline to Day 330 (Year 1)"; 2029-04-15
NCT06597019
"Study to Evaluate Efficacy and Safety of Inclisiran in Children With Heterozygous Familial Hypercholesterolemia"; n 60; "Percentage change in LDL-C from baseline to Day 330 (Year 1)"; 2029-04-15
NCT06770543
"Leqvio rPMS (Regulatory Post-Marketing Surveillance in Korea)"; n 1500; "Incidences of adverse events/adverse drug reactions (AEs/ADRs)"; 2031-01-02
recorded 2026-09-01 · last checked 2026-09-04
Q9
Which 5 trials of Inclisiran posted no result?
Posted no result
5 of 5 completed trials
Registrations
NCT02314442, NCT03159416, NCT04774003, NCT05974345 and NCT05118230
Completion dates
oldest 2015-11; newest 2024-07-20
Show the evidence
Trial
NCT02314442
2015-11
NCT03159416
2018-03-24
NCT04774003
2021-10-18
NCT05974345
2023-12-15
NCT05118230
2024-07-20
Q10
At the median, Inclisiran's trials enrolled 329 people — anything larger?
Median enrolment
329
Largest enrolment
204691
Registered trials counted
60
Q11
What do 35 spontaneous reports say about Inclisiran — 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.
Inclisiran appears in spontaneous reports to regulators. Across the 10 most-reported reaction terms, 35 reaction mentions were counted: myalgia 6; myopathy 6; hypertriglyceridaemia 5; therapeutic product effect incomplete 5. open-targets-adr · CHEMBL5095052 · 2026-06-24
Show the evidence
myalgia
6
myopathy
6
hypertriglyceridaemia
5
therapeutic product effect incomplete
5
peripheral arterial occlusive disease
3
ischaemic nephropathy
2
4 more recorded rows
leriche syndrome
2
peripheral artery bypass
2
spleen ischaemia
2
ulnar nerve injury
2
recorded 2026-06-24 · last checked 2026-09-04
Q12
Was Inclisiran studied with fasting?
fasting is named in Inclisiran's label sentences: "VICTORION-Mono (V-Mono), a 6-month, randomized, double-blind, multicenter, placebo- and active-comparator controlled phase 3 trial, assessed inclisiran monotherapy in adult participants (aged 18-75 years) without prior ASCVD, diabetes, or familial hypercholesterolemia, with a fasting LDL-C of…" openfda-label+europepmc · 2025-05-05
1 recorded statement; fasting
Show the evidence
fasting
VICTORION-Mono (V-Mono), a 6-month, randomized, double-blind, multicenter, placebo- and active-comparator controlled phase 3 trial, assessed inclisiran monotherapy in adult participants (aged 18-75 years) without prior ASCVD, diabetes, or familial hypercholesterolemia, with a fasting LDL-C of 100-190 mg/dL and 10-year predicted ASCVD risk of <7.5% according to pooled cohort equation, who were not…
recorded 2025-05-05 · last checked 2026-09-04
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 · Open Targets 26.06 — CC0 · derived from this page's own recorded fields; no external licence · mixed register set; per-register licences in docs/specs/corpus-20k-sources.md · openFDA / DailyMed — US Government work
✗ required summary fields resolved: 5 required field(s) not terminal: Why people use it, Best-supported result, Most important common problem, Biggest unanswered question, Human evidence
✓ public claims reviewed: 0 reviewed claim(s); drafts are never rendered
✓ source coverage passed: 9 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
This is a record of evidence. It is not medical advice, and it does not say this substance suits you. Nothing here says any substance on RNAWiki is appropriate for a child.