This page shows what was measured, who it was measured in, and what that does not settle.
What Zilebesiran does in the body
Zilebesiran stops the liver making the starting material at all.
Your body makes a hormone chain that tightens blood vessels, and it starts with a protein the liver produces called angiotensinogen. Most blood pressure pills interrupt that chain somewhere in the middle. One injection lowers blood pressure for three to six months, which solves the problem of forgotten tablets and creates a new one: if the pressure needs to come back up quickly, there is no way to make that happen.
Why people take it. Studied as a twice-yearly injection for high blood pressure.
What happened in people
One injection lowered the top blood-pressure number by about 15 points more after three months.
✓ 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
Studies have measured blood pressure, not whether treatment prevents strokes or heart attacks.
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.
What the registries record it as
The substance registry classes this as nucleicacid.
FDA substance registry · E422BH4BRK · read 2026-08-29
Where each sentence above came from
A person wrote this explanation into the record, with the studies named in the path below.
A reviewer approved this sentence against this exact record and its sources.
The limit a reviewer approved as the one that matters most here.
The four opening statements run to 105 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.
Absolute difference
An absolute difference is how many more people in a hundred were affected.
A picture of it, and where the picture fails
It is like counting heads in two rooms of a hundred.
Where that stops being true. Heads are easy to count. Study results carry a margin of error too.
What people get wrong. It is confused with a percentage change, which can look far larger.
The arithmetic difference in event rates between arms.
Confidence interval
A confidence interval is the range the true answer is likely to sit in.
A picture of it, and where the picture fails
It is like a weather forecast giving a range rather than one number.
Where that stops being true. A forecast range covers tomorrow. This one covers what the study could resolve.
What people get wrong. The middle number is read as the answer. A range crossing zero means no change is still possible.
An interval estimate that would contain the true parameter in a stated proportion of repeated studies.
What happened in people◇Read from sources, not yet reviewed
What happened in people
Each card is one study: the exact question it asked, who was in it, and whether it showed what it set out to show.
Safety, pharmacokinetics and pharmacodynamics of single ascending doses
✓ The study showed what it set out to show
Who was studied
Phase 1 (NCT03934307)
How many people
107
Study design
Phase 1
Compared against
Not recorded for this study
Kind of result
A number that stands in for health
What was found
Dose correlation with serum angiotensinogen reduction r = -0.56 (95% CI -0.69 to -0.39) at week 8
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. Five patients had mild transient injection-site reactions. No hypotension, hyperkalaemia or renal deterioration requiring intervention at this stage — signals that did appear in the larger phase 2 studies.
How far it carries. This study is recorded from the curated record, not from the registry match.
Form and route. GalNAc-conjugated siRNA, subcutaneous injection (investigational)
Interval reported. 95% CI -0
Written into the record, not signed off as a reviewed claim.
Difference versus placebo in change from baseline to 3 months in 24-hour mean ambulatory systolic blood pressure, within each background-therapy cohort
✓ The study showed what it set out to show
Who was studied
KARDIA-2 (NCT05103332)
How many people
663
Study design
Phase 2
Compared against
Not recorded for this study
Kind of result
A number that stands in for health
What was found
P < .001 (indapamide and amlodipine cohorts); P = .02 (olmesartan cohort)
Repeated elsewhere
Partially Replicated
What this does not prove. Meeting one endpoint in one population does not carry to other goals or other people.
The limits of this study, and where it came from
Main limit. Hyperkalaemia 5.5% versus 1.8%, hypotension 4.3% versus 2.1% and acute kidney failure 4.9% versus 1.5% against placebo.
How far it carries. This study is recorded from the curated record, not from the registry match.
Form and route. GalNAc-conjugated siRNA, subcutaneous injection (investigational)
Interval reported. Not recorded in this summary
Written into the record, not signed off as a reviewed claim.
RNAWiki holds 3 written-up human studies for this substance, each with the question it asked.
How we know it
Each card names the study, the number of people and what the study set out to measure.
What this does not prove
These summaries were written by a person and have not been signed off as reviewed claims.
Why it matters
A study that failed is as informative as one that worked, and both are here.
What we still do not know
No reviewed claim exists, so no exact population, effect size or interval is published yet.
What it changes in the body◇Read from sources, not yet reviewed
The path through the body
From what a person takes to what changes. A solid line is a step measured in people. A dashed line is a step nobody has measured that way.
Start
Zilebesiran
What a person takes: GalNAc-conjugated siRNA, subcutaneous injection (investigational).
The measurement behind this step
A single subcutaneous injection, studied at 150 mg, 300 mg and 600 mg every six months and 300 mg every three months. The announced phase 3 outcome trial uses 300 mg every six months. No approved presentation exists.
Getting in
One subcutaneous injection every three to six months
A single injection under the skin. The sugar tag sends it to the liver, which is where the starting material for the blood-pressure hormone chain is made.
╌╌Described, with no measurement named. No measurement is named for this step, so it is drawn as an unconfirmed link.
The measurement behind this step
A GalNAc-conjugated duplex binds hepatocyte ASGPR. Doses of 150 to 600 mg have been studied at three- and six-monthly intervals; the phase 3 outcome trial uses 300 mg every six months.
Uptake into the hepatocyte and a months-long reservoir
The liver cell absorbs the drug and holds a store that releases slowly, which is why one dose 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
ASGPR-mediated endocytosis routes the conjugate to the endosome; a fraction escapes to the cytoplasm and the endolysosomal depot sustains angiotensinogen suppression for months after plasma clearance.
The active strand enters the cell's silencing machinery. No sequence has been published for this drug, so this page describes the mechanism rather than the letters.
╌╌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 antisense strand loads into Argonaute 2 within RISC and directs it to AGT transcripts. No nucleotide sequence for zilebesiran has been published in a verifiable source, so none is recorded and the structure carries no machine-verification badge.
AGT messenger RNA is cut and the cascade loses its substrate
The complex destroys the instructions for angiotensinogen. Renin can still work, but it has nothing left to work on.
╌╌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
Argonaute 2 cleaves AGT mRNA, reducing hepatic angiotensinogen secretion. Angiotensinogen is the sole precursor of every angiotensin peptide, so removing it depletes the cascade at its source rather than blocking one enzyme or one receptor downstream. Serum angiotensinogen reduction correlated with dose in the phase 1 study.
Blood pressure falls for months, and cannot be raised back quickly
Twenty-four-hour average pressure dropped by about 15 mmHg more than placebo and stayed down. The same durability means there is no way to switch the effect off if it becomes unwanted.
╌╌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
Sustained angiotensinogen depletion produced placebo-adjusted 24-hour ambulatory systolic reductions of 14.1 to 16.7 mmHg at month 3, consistent through the diurnal cycle and sustained to 24 weeks. Hyperkalaemia, hypotension and acute kidney failure were each roughly three times more common than placebo in KARDIA-2, and none of them can be addressed by stopping the drug.
No suggested links are held for this record, so nothing is hidden from this path.
What we know
The record describes 5 steps from taking it to an effect in a person.
How we know it
Each step names the study behind it in the technical detail beside it.
What this does not prove
A change inside the body is a reason to look. It is not a result in a person.
Why it matters
A reader can see exactly where the chain stops being measured in people.
What we still do not know
No reviewed claim binds any of these steps to a named population.
What is missing or unclear◇Read from sources, not yet reviewed
Were people like you studied?
RNAWiki cannot tell whether a study fits you. It can show who was in it, and where the result stops carrying.
Who was studied
People similar to this profile were included.
In trials so far, adults with mild to moderate hypertension after antihypertensive washout, and adults whose blood pressure remains uncontrolled on one or more standard agents.
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
The effect size fell from roughly 16 mmHg after washout to 4.5 mmHg on top of an angiotensin receptor blocker, because both act on the same pathway
This is a scope explorer, not a diagnosis engine.
It shows who was studied so you can see whether people similar to you were included.
RNAWiki cannot tell whether a study fits you. It can show who was in it.
What it would be like to take◇Read from sources, not yet reviewed
Why it might seem to do nothing
A real effect and a noticed effect are different things. These are the recorded reasons the two come apart.
It was studied in different people
The people in the studies were not much like the reader.
On this record: Which groups were under-represented in the studies has not been recorded for this substance. Pregnancy, breastfeeding, children, older adults, and people with liver or kidney conditions are commonly excluded from trials; nothing here says whether they were.
The evidence may simply be wrong
Small early studies often do not hold up.
On this record: RNAWiki has not yet published a reviewed conclusion for this use.
Other reasons RNAWiki checked and found nothing for (11)
It was studied for a different goal
The studies measured something else entirely. Nothing in this record points to this reason.
A different form was studied
The studied form is not the form on the shelf. Nothing in this record points to this reason.
There was nothing to correct
Where a level is already normal, topping it up may change nothing. Nothing in this record points to this reason.
Something else had to happen too
In the studies it was paired with training, a diet or another treatment. Nothing in this record points to this reason.
The change is too small to feel
A real change can still sit below what a person notices. Nothing in this record points to this reason.
Day-to-day swing hides it
Sleep, food, stress and time of day move most numbers more than this would. Nothing in this record points to this reason.
Not enough time yet
The studies ran longer than the person has waited. Nothing in this record points to this reason.
It was not taken as studied
Missed days change the result, and studies count them. Nothing in this record points to this reason.
Something else changed at the same time
Two changes at once cannot be told apart afterwards. Nothing in this record points to this reason.
The product may not be what it says
Contents of a sold product are not always what the label states. Nothing in this record points to this reason.
No recorded reason
RNAWiki has nothing stored that would explain it. Nothing in this record points to this reason.
None of these is a reason to take more. Taking more is not a step this page ever suggests.
What it would be like to take◇Read from sources, not yet reviewed
What taking it involves
The recorded facts about getting hold of it and using it. Nothing here is a suggestion about what you should do.
How it is supplied
Still being tested
❝ 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
A single subcutaneous injection, studied at 150 mg, 300 mg and 600 mg every six months and 300 mg every three months. The announced phase 3 outcome trial uses 300 mg every six months. No approved presentation exists.
✎ 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
Not recorded.
∅ Nothing recorded
Where this came from
RNAWiki holds nothing here and says so rather than guessing.
No register entry is recorded.
No source is stored against this line.
Why people stop
Not recorded.
∅ Nothing recorded
Where this came from
RNAWiki holds nothing here and says so rather than guessing.
No record of why people stopped taking it is stored for this substance.
No source is stored against this line.
What it would be like to take◇Read from sources, not yet reviewed
What can go wrong
Sorted by where each line came from. A regulator's label and a report somebody sent in are not the same kind of fact.
·Worth asking a clinician aboutWritten into the record from the studies named on this page
No FDA label and therefore no labelled warning set. In KARDIA-1, adverse events occurred in 60.9% of zilebesiran patients versus 50.7% on placebo, with serious events less frequent on drug (3.6% versus 6.7%). In the larger KARDIA-2 study hyperkalaemia (5.5% versus 1.8%), hypotension (4.3% versus 2.1%) and acute kidney failure (4.9% versus 1.5%) were all more common than placebo, though most episodes were described as mild and resolved without medical intervention.
Nobody counted how many people took this and were fine, so this cannot be turned into a rate.
Over a long time. No completed tested study window is recorded, so long-term effects are not established by the registry record.
Groups the studies covered thinly. Which groups were under-represented in the studies has not been recorded for this substance. Pregnancy, breastfeeding, children, older adults, and people with liver or kidney conditions are commonly excluded from trials; nothing here says whether they were.
What is missing or unclear∅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.
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
The announced phase 3 outcome trial uses 300 mg every six months. No approved presentation exists.
✎ 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. The questions below are for a clinician or pharmacist.
Questions worth asking
Which of the trials of Zilebesiran 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 blood pressure reduction reduces strokes, heart attacks or death — no outcome trial has reported
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 KARDIA-1 monotherapy effect size applies to patients already on renin-angiotensin blockade; KARDIA-2 shows it does not
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 KARDIA-3's office systolic reduction can be compared with KARDIA-1's ambulatory figures — they are different measurements
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 Zilebesiran 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.
KARDIA-1: 14 to 17 mmHg placebo-adjusted reduction from a single injection
In plain words
One injection lowered 24-hour average systolic pressure by about 15 mmHg more than placebo at three months, across every dose tested.
What was measured
24-hour mean ambulatory systolic blood pressure at month 3
Effect estimate
No reviewed effect estimate exists for this record.
Limits
See the technical detail.
From the source
Phase 2, randomised, double-blind, dose-ranging, 78 sites in 4 countries, 394 randomised and 377 in the full analysis set. Least-squares mean differences versus placebo in change from baseline to month 3 in 24-hour mean ambulatory systolic pressure: -14.1 mmHg (150 mg every 6 months), -16.7 mmHg (300 mg every 3 or 6 months) and -15.7 mmHg (600 mg every 6 months), all P<.001. Over 6 months, adverse events occurred in 60.9% of zilebesiran patients versus 50.7% of placebo, serious adverse events in 3.6% versus 6.7%, and non-serious drug-related events in 16.9% versus 8.0%, principally injection-site reactions and mild hyperkalaemia.
Written into the record, not signed off as a reviewed claim
KARDIA-2: the added effect shrinks to 4.5 mmHg on top of an ARB
In plain words
On top of a diuretic, zilebesiran added 12.1 mmHg. On top of a calcium channel blocker, 9.7. On top of a drug already blocking the same hormone pathway, only 4.5.
What was measured
24-hour mean ambulatory systolic blood pressure at 3 months, by background agent
Effect estimate
No reviewed effect estimate exists for this record.
Limits
See the technical detail.
From the source
Phase 2, 150 sites in 8 countries. 1,491 patients entered an open-label run-in on indapamide 2.5 mg, amlodipine 5 mg or olmesartan 40 mg; 663 with 24-hour ambulatory systolic pressure of 130 to 160 mmHg were randomised 1:1 to a single subcutaneous 600 mg dose of zilebesiran or placebo. Least-squares mean differences at 3 months: -12.1 mmHg (indapamide, 95% CI -16.5 to -7.6, P<.001), -9.7 mmHg (amlodipine, 95% CI -12.9 to -6.6, P<.001) and -4.5 mmHg (olmesartan, 95% CI -8.2 to -0.8, P=.02). Hyperkalaemia occurred in 5.5% versus 1.8%, hypotension in 4.3% versus 2.1% and acute kidney failure in 4.9% versus 1.5%.
Written into the record, not signed off as a reviewed claim
No cardiovascular outcome has been measured, and the phase 3 trial has not reported
In plain words
Everything measured so far is blood pressure. Whether that translates into fewer strokes and heart attacks is the point of a trial that was only announced in August 2025.
What was measured
That a 15 mmHg ambulatory systolic reduction from an siRNA reduces cardiovascular events as it does from a daily tablet
Effect estimate
No reviewed effect estimate exists for this record.
Limits
See the technical detail.
From the source
All completed zilebesiran studies are phase 1 or phase 2 with blood pressure endpoints. Roche and Alnylam announced in August 2025 that ZENITH, a cardiovascular outcome trial of approximately 11,000 patients comparing zilebesiran 300 mg every six months against placebo in uncontrolled hypertension with established or high cardiovascular risk on two or more antihypertensives including a diuretic, would proceed. Blood pressure reduction has a strong outcome track record across drug classes, but it has never been established for this class.
Source
Roche media release, 30 August 2025; Bakris GL et al., JAMA 2024;331:740-749
Role in the trial
Not matched to a registered study
Identity check
no open identity hold
Audit mark
caution
Review state
Written into the record, not signed off as a reviewed claim
The dosing interval is also the problem: the effect cannot be withdrawn
In plain words
A pill can be stopped today. An injection that works for six months cannot. If a patient becomes dehydrated, septic or hypotensive, the drug is still working.
What was measured
Not recorded
Effect estimate
No reviewed effect estimate exists for this record.
Limits
This entry records a failure.
From the source
Zilebesiran produces sustained angiotensinogen suppression from a single dose, with blood-pressure effects consistent through the diurnal cycle and sustained at 24 weeks in the phase 1 study. A 2026 review frames the unresolved clinical question directly: how acute illness should be managed when upstream renin-angiotensin suppression cannot be rapidly attenuated. The safety signals that make this concrete are already visible — hyperkalaemia in 5.5%, hypotension in 4.3% and acute kidney failure in 4.9% of KARDIA-2 patients, against 1.8%, 2.1% and 1.5% on placebo.
Written into the record, not signed off as a reviewed claim
The effect depends on dietary salt and on background therapy
In plain words
A high-salt diet blunts the drug and an angiotensin blocker amplifies it. This is a treatment whose size depends on what else the patient is doing.
What was measured
Change in 24-hour ambulatory blood pressure under low- and high-salt conditions and with irbesartan
Effect estimate
No reviewed effect estimate exists for this record.
Limits
See the technical detail.
From the source
The phase 1 study enrolled 107 patients across single ascending doses of 10 to 800 mg. Part B assessed the 800 mg dose under low- and high-salt diets and Part E in combination with irbesartan; the results were consistent with attenuation of the blood-pressure effect by a high-salt diet and augmentation by coadministration with an angiotensin receptor blocker. Serum angiotensinogen reduction correlated with dose (r = -0.56 at week 8; 95% CI -0.69 to -0.39).
Written into the record, not signed off as a reviewed claim
The number gets smaller as the population gets harder
In plain words
Sixteen millimetres of mercury in patients washed off their medication. Four and a half on top of an ARB. Five in a higher-risk group on multiple drugs, with a p-value of 0.043.
What was measured
Not recorded
Effect estimate
No reviewed effect estimate exists for this record.
Limits
See the technical detail.
From the source
KARDIA-1 measured 24-hour ambulatory systolic pressure after antihypertensive washout and reported differences of 14.1 to 16.7 mmHg. KARDIA-2 measured the same endpoint on top of a single background agent and reported 12.1, 9.7 and 4.5 mmHg depending on which. Roche and Alnylam reported that KARDIA-3, in patients with established or high cardiovascular risk on two or more antihypertensives, produced a placebo-adjusted office systolic reduction of -5.0 mmHg at the month-3 primary endpoint (p=0.0431) in a cohort of 270 randomised patients. Note that KARDIA-3 reports an office measurement while KARDIA-1 and KARDIA-2 report 24-hour ambulatory measurements, so the three numbers are not directly comparable.
Source
Bakris GL et al., JAMA 2024; Desai AS et al., JAMA 2025; Roche media release, 30 August 2025
Role in the trial
Not matched to a registered study
Identity check
no open identity hold
Audit mark
contested
Review state
Written into the record, not signed off as a reviewed claim
Where else this substance is registered
FDA substance identifier (UNII)
E422BH4BRK
CAS registry number
2380166-33-4
WHO international nonproprietary name list entry
11531
EMA substance identifier
300000037422
Checks this page had to pass
✓ Passed
Identity resolved
no open identity hold
✓ Passed
No unresolved merge across substance families
no quarantine open
✓ Passed
Every public sentence names a source
The opening statement carries the origin: Written into the record, not signed off.
✗ Not passed
Trial roles classified for highlighted evidence
No registered study is classified as testing this substance.
✓ Passed
No internal keys in reader text
enforced by the copy-contract test over the rendered page
✓ Passed
Safety mode resolved
The identity record classes it as siRNA (Small Interfering RNA).
✓ Passed
Canonical metadata present
slug and display name present
What is missing or unclear◇Read from sources, not yet reviewed
What to learn next
Ordered by what would most change how you read this page, starting with what is easiest to misunderstand.
This order is fixed in code and does not count clicks or time on the page.
What is not here
8 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 was measured, goal by goal — found nothing in the sources checked.
How close this is to real life — found nothing in the sources checked.
Felt, measured, or meaningful — found nothing in the sources checked.
How long anything takes — found nothing in the sources checked.
What it may clash with — found nothing in the sources checked.
Other ways to the same goal — found nothing in the sources checked.
How this medicine reached us — found nothing in the sources checked.
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.
Silences hepatic angiotensinogen at the top of the blood-pressure cascade, lowering 24-hour ambulatory systolic pressure by 14 to 17 mmHg against placebo at three months from a single injection — with hyperkalaemia and acute kidney injury signals, and an effect that cannot be switched off for six months.
Recorded evidence blocks (3)
Q1
Which one trial of Zilebesiran posted no result?
Posted no result
1 of 1 completed trials
Registrations
NCT03934307
Completion dates
oldest 2023-01-04
Show the evidence
TrialNCT03934307
2023-01-04
Q2
At the median, Zilebesiran's trials enrolled 375 people — anything larger?
Median enrolment
375
Largest enrolment
11000
Registered trials counted
7
Q3
Who carried Zilebesiran to phase 3?
Alnylam Pharmaceuticals, 7 studies: the lead sponsor the registry names most often for Zilebesiran; highest registry phase 3, 1 of 7 studies at it. ClinicalTrials.gov · 2026-09-01
✗ 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: 3 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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