This page shows what was measured, who it was measured in, and what that does not settle.
What Givosiran does in the body
Givosiran tells liver cells to stop making the machine that starts the line, so the pile-up never forms.
Your liver builds haem on an assembly line. In acute porphyria one station is broken, so when the line speeds up the half-finished parts pile up, and those parts are poisonous to nerves. Attacks became about four times less frequent in the trial, though liver enzymes and kidney measurements moved more often on treatment than on placebo.
Why people take it. Acute porphyria attacks — severe abdominal pain crises
What happened in people
Lower urinary aminolevulinic acid and porphobilinogen, fewer days of haemin use, better daily worst-pain scores
✎ Source-linked record
Where this came from
A person wrote this into the record with the study named beside it. No reviewer has signed it off.
The recorded finding that sits closest to something a person would notice. Written into the record, not signed off, and it carries no population or interval.
ENVISION (NCT03338816) · a recorded source, not a stored snapshot
GIVLAARI (givosiran) injection, US prescribing information — DailyMed (https://dailymed.nlm.nih.gov/dailymed/drugInfo.cfm?setid=167e663c-11e1-497b-a3fc-951d6… · a recorded source, not a stored snapshot
The limit that matters most
In the FAERS comparison covering 2019 to 2023, acute porphyria itself was the most common reported reaction category for givosiran at 32.7% of cases — that is a report of the underlying disease, not necessarily a drug effect, and it illustrates how hard passive surveillance is to read in a rare disease
Where it acts
Hepatocyte cytoplasm (liver)
Kind of result
Symptoms and quality of life
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 · ROV204583W · 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.
The recorded use, written for a reader without medical training. Not signed off.
A limit recorded against this substance. Not signed off as a reviewed claim.
The four opening statements run to 97 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.
Protein
A protein is a folded chain your body builds to do a specific job.
A picture of it, and where the picture fails
A protein is like a tool bent into one shape for one task.
Where that stops being true. A tool keeps its shape. A protein can change shape and stop working.
What people get wrong. Protein in food and a protein in the body are related but not the same thing.
A polymer of amino acids folded into a defined structure that determines its function.
Gene
A gene is a stretch of instructions for building one protein.
A picture of it, and where the picture fails
A gene is like one page of a building plan.
Where that stops being true. A page is read the same way every time. A gene can be read more or less often.
What people get wrong. Having a gene is often read as having a trait. Whether it is used matters as much.
A segment of DNA that encodes a functional product, usually a protein.
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.
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.
Annualised rate of composite porphyria attacks over 6 months in acute intermittent porphyria
✓ The study showed what it set out to show
Who was studied
ENVISION (NCT03338816)
How many people
94
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
Unreplicated
What this does not prove. Meeting one endpoint in one population does not carry to other goals or other people.
The limits of this study, and where it came from
Main limit. Aminotransferase elevations, serum creatinine and eGFR changes, and injection-site reactions were all more frequent with givosiran; the trial authors state the efficacy came with more hepatic and renal adverse events.
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
Interval reported. Not recorded in this summary
Written into the record, not signed off as a reviewed claim.
ENVISION (NCT03338816) · a recorded source, not a stored snapshot
GIVLAARI (givosiran) injection, US prescribing information — DailyMed (https://dailymed.nlm.nih.gov/dailymed/drugInfo.cfm?setid=167e663c-11e1-497b-a3fc-951d6… · 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 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
Givosiran
What a person takes: GalNAc-conjugated siRNA, subcutaneous injection.
The measurement behind this step
A 1 mL single-dose vial containing 189 mg of givosiran, dosed at 2.5 mg/kg of actual body weight once monthly by subcutaneous injection, with dose reduction to 1.25 mg/kg after a significant transaminase elevation that then improves.
Getting in
Monthly subcutaneous dose with a liver-specific tag
An injection under the skin once a month, dosed by body weight. Three sugar molecules on the drug make liver cells grab it and almost nothing else does.
╌╌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
Triantennary N-acetylgalactosamine (L96) on the sense strand binds the hepatocyte asialoglycoprotein receptor. The label dose is 2.5 mg/kg monthly, with reduction to 1.25 mg/kg after significant transaminase elevation.
ENVISION (NCT03338816) · a recorded source, not a stored snapshot
GIVLAARI (givosiran) injection, US prescribing information — DailyMed (https://dailymed.nlm.nih.gov/dailymed/drugInfo.cfm?setid=167e663c-11e1-497b-a3fc-951d6… · a recorded source, not a stored snapshot
Reaching the cell
Endocytosis into the hepatocyte
The liver cell swallows the drug into an internal compartment, and a fraction leaks out into the working part of the cell.
╌╌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
ASGPR-mediated clathrin endocytosis routes the duplex to the endosome, where the receptor releases its cargo at acidic pH and recycles. A small proportion escapes to the cytoplasm and is available for RISC loading.
ENVISION (NCT03338816) · a recorded source, not a stored snapshot
GIVLAARI (givosiran) injection, US prescribing information — DailyMed (https://dailymed.nlm.nih.gov/dailymed/drugInfo.cfm?setid=167e663c-11e1-497b-a3fc-951d6… · a recorded source, not a stored snapshot
What it acts on
Guide strand loaded into the silencing complex
The two strands split; one is loaded into the cell's gene-silencing machinery and the other is discarded.
╌╌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 loads into Argonaute 2 within RISC. The extensive 2'-F and 2'-OMe substitution and the six phosphorothioate linkages give it the nuclease resistance to survive long enough to be loaded.
ENVISION (NCT03338816) · a recorded source, not a stored snapshot
GIVLAARI (givosiran) injection, US prescribing information — DailyMed (https://dailymed.nlm.nih.gov/dailymed/drugInfo.cfm?setid=167e663c-11e1-497b-a3fc-951d6… · a recorded source, not a stored snapshot
The change it makes
ALAS1 messenger RNA is cut inside its coding body
The complex finds the instructions for the enzyme that starts the haem assembly line, and cuts them.
╌╌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
Unusually for this class, the guide binds the coding sequence of ALAS1 mRNA with near-complete complementarity rather than a 3' untranslated region, and Argonaute 2 catalyses cleavage. Reduced ALAS1 protein means reduced flux into the haem pathway upstream of the deficient enzyme.
ENVISION (NCT03338816) · a recorded source, not a stored snapshot
GIVLAARI (givosiran) injection, US prescribing information — DailyMed (https://dailymed.nlm.nih.gov/dailymed/drugInfo.cfm?setid=167e663c-11e1-497b-a3fc-951d6… · a recorded source, not a stored snapshot
What that does for a person
The toxic intermediates stop accumulating and attacks become rarer
With the assembly line slowed at its start, the poisonous half-finished parts stop piling up. Attacks fell from about 12.5 a year to about 3.2.
╌╌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
Lower ALAS1 activity reduces production of aminolevulinic acid and porphobilinogen, the neurotoxic intermediates that accumulate behind the deficient downstream enzyme. Urinary levels of both fell in ENVISION alongside the attack-rate reduction, haemin use and daily worst-pain scores.
ENVISION (NCT03338816) · a recorded source, not a stored snapshot
GIVLAARI (givosiran) injection, US prescribing information — DailyMed (https://dailymed.nlm.nih.gov/dailymed/drugInfo.cfm?setid=167e663c-11e1-497b-a3fc-951d6… · a recorded source, not a stored snapshot
No suggested links are held for this record, so nothing is hidden from this path.
What we know
The record describes 5 steps from taking it to an effect in a person.
How we know it
Each step names the study behind it in the technical detail beside it.
What this does not prove
A change inside the body is a reason to look. It is not a result in a person.
Why it matters
A reader can see exactly where the chain stops being measured in people.
What we still do not know
No reviewed claim binds any of these steps to a named population.
What is missing or unclear◇Read from sources, not yet reviewed
Were people like you studied?
RNAWiki cannot tell whether a study fits you. It can show who was in it, and where the result stops carrying.
Who was studied
People similar to this profile were included.
Adults with acute hepatic porphyria, most of whom have acute intermittent porphyria, the commonest subtype.
Who is missing from the studies
Which groups were under-represented in the studies has not been recorded for this substance. Pregnancy, breastfeeding, children, older adults, and people with liver or kidney conditions are commonly excluded from trials; nothing here says whether they were.
What the label states about particular groups
On pediatric, the label states: “Safety and effectiveness in pediatric patients have not been established.”
US prescribing information · 167e663c-11e1-497b-a3fc-951d65d58eaa · read 2026-08-30
On older people, the label states: “Clinical studies of GIVLAARI did not include sufficient numbers of patients aged 65 and over to determine whether they respond differently from younger patients.”
US prescribing information · 167e663c-11e1-497b-a3fc-951d65d58eaa · read 2026-08-30
On people who are pregnant, the label states: “Risk Summary In animal reproduction studies, subcutaneous administration of givosiran to pregnant rabbits during the period of organogenesis resulted in adverse developmental outcomes at doses that produced maternal toxicity (see Data ).”
US prescribing information · 167e663c-11e1-497b-a3fc-951d65d58eaa · read 2026-08-30
On people who are breastfeeding, the label states: “Risk Summary There are no data on the presence of GIVLAARI in human milk, the effects on the breastfed child, or the effects on milk production.”
US prescribing information · 167e663c-11e1-497b-a3fc-951d65d58eaa · read 2026-08-30
Where the result stopped carrying
Chronic intravenous haemin prophylaxis, the prior standard, requires venous access that frequently fails and carries phlebitis as its most commonly reported adverse reaction
This is a scope explorer, not a diagnosis engine.
It shows who was studied so you can see whether people similar to you were included.
RNAWiki cannot tell whether a study fits you. It can show who was in it.
What it would be like to take◇Read from sources, not yet reviewed
Why it might seem to do nothing
A real effect and a noticed effect are different things. These are the recorded reasons the two come apart.
It was studied in different people
The people in the studies were not much like the reader.
On this record: Which groups were under-represented in the studies has not been recorded for this substance. Pregnancy, breastfeeding, children, older adults, and people with liver or kidney conditions are commonly excluded from trials; nothing here says whether they were.
The evidence may simply be wrong
Small early studies often do not hold up.
On this record: RNAWiki has not yet published a reviewed conclusion for this use.
Other reasons RNAWiki checked and found nothing for (11)
It was studied for a different goal
The studies measured something else entirely. Nothing in this record points to this reason.
A different form was studied
The studied form is not the form on the shelf. Nothing in this record points to this reason.
There was nothing to correct
Where a level is already normal, topping it up may change nothing. Nothing in this record points to this reason.
Something else had to happen too
In the studies it was paired with training, a diet or another treatment. Nothing in this record points to this reason.
The change is too small to feel
A real change can still sit below what a person notices. Nothing in this record points to this reason.
Day-to-day swing hides it
Sleep, food, stress and time of day move most numbers more than this would. Nothing in this record points to this reason.
Not enough time yet
The studies ran longer than the person has waited. Nothing in this record points to this reason.
It was not taken as studied
Missed days change the result, and studies count them. Nothing in this record points to this reason.
Something else changed at the same time
Two changes at once cannot be told apart afterwards. Nothing in this record points to this reason.
The product may not be what it says
Contents of a sold product are not always what the label states. Nothing in this record points to this reason.
No recorded reason
RNAWiki has nothing stored that would explain it. Nothing in this record points to this reason.
None of these is a reason to take more. Taking more is not a step this page ever suggests.
What it would be like to take◇Read from sources, not yet reviewed
What taking it involves
The recorded facts about getting hold of it and using it. Nothing here is a suggestion about what you should do.
How it is supplied
Given by a clinician
❝ Quoted from a source
Where this came from
Copied from a source RNAWiki stored, with the source named.
Read from the recorded approval status.
No source is stored against this line.
Form and route
GalNAc-conjugated siRNA, subcutaneous injection
✎ 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.
The identity record classes it as siRNA (Small Interfering RNA).
No source is stored against this line.
What is in the pack
25 mg/kg after a significant transaminase elevation that then improves.
✎ 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
Labelled warnings for anaphylaxis, hepatic toxicity with baseline and periodic liver testing, renal toxicity, injection-site reactions including recall reactions, increased blood homocysteine and pancreatitis. Nausea and injection-site reactions each occur in at least 20% of patients.
Nobody counted how many people took this and were fine, so this cannot be turned into a rate.
ENVISION (NCT03338816) · a recorded source, not a stored snapshot
GIVLAARI (givosiran) injection, US prescribing information — DailyMed (https://dailymed.nlm.nih.gov/dailymed/drugInfo.cfm?setid=167e663c-11e1-497b-a3fc-951d6… · a recorded source, not a stored snapshot
Over a long time. No completed tested study window is recorded, so long-term effects are not established by the registry record.
Groups the studies covered thinly. Which groups were under-represented in the studies has not been recorded for this substance. Pregnancy, breastfeeding, children, older adults, and people with liver or kidney conditions are commonly excluded from trials; nothing here says whether they were.
What is missing or unclear◇Read from sources, not yet reviewed
Does the exact form matter?
Evidence belongs to the exact thing that was tested. A different salt, a different mixture or a different preparation is a different question.
The form that was studied
GalNAc-conjugated siRNA, subcutaneous injection
✎ 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
25 mg/kg after a significant transaminase elevation that then improves.
✎ 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
2 products list this as an active ingredient in the United States drug directory. 2 of them contain it and nothing else.
FDA National Drug Code directory · 71336-1001 · read 2026-08-29
They are sold as injection, solution and powder, taken subcutaneous.
FDA National Drug Code directory · 71336-1001 · read 2026-08-29
The regulator's established pharmacologic class for it is aminolevulinate synthase 1-directed rna interaction [epc], decreased rna integrity [pe] and rna.
FDA National Drug Code directory · 71336-1001 · 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 · 167e663c-11e1-497b-a3fc-951d65d58eaa · read 2026-08-29
Those labels are classed as human prescription drug.
US prescribing information · 167e663c-11e1-497b-a3fc-951d65d58eaa · read 2026-08-29
GIVLAARI is subcutaneous at 3 DOSAGE FORMS AND STRENGTHS Injection: 189 mg/mL clear, colorless-to-yellow solution in a single-dose vial Injection: 189 mg/mL in a single-dose vial., recorded as fda label in effect 2025-09-10 in the United States.
US prescribing information · 167e663c-11e1-497b-a3fc-951d65d58eaa · read 2026-08-30
Evidence carries across two names for one substance. It does not carry across a salt, a mirror form or a mixture.
What it would be like to take◇Read from sources, not yet reviewed
What you could measure
This one is decided with a clinician, so this section holds questions to ask rather than a plan to run.
Self-experiment planning is not offered for a prescription or clinician-supervised medicine. The questions below are for a clinician or pharmacist.
Questions worth asking
Which of the trials of Givosiran 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 six months of attack reduction predicts fewer long-term neurological, renal or hepatic complications
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 labelled homocysteine elevation is clinically inert — nobody has measured what it does over years
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 attack-rate benefit generalises beyond acute intermittent porphyria, which supplied 89 of the 94 randomised patients
Why it sounds right. It follows from something real on this page: a body step, an animal result or a related finding.
The missing step. Nobody measured this in people for this use, or the study that did measure it did not show it.
What would change this
A study in people, for this exact use, measuring this exact thing, that a reviewer signs off.
RNAWiki has not yet published a reviewed conclusion for this use.
What is missing or unclear◇Read from sources, not yet reviewed
What nobody knows yet
Open questions, each with why it is open and what would close it.
How much did people take in the studies?
The sources RNAWiki checked hold nothing for this field.
Why it matters. A result belongs to an amount. Without the amount the result floats free.
What would answer it
A stored source that records it, and a reviewer to sign it off.
Last checked 2026-09-04. Searched: The sources listed in the receipts at the foot of this page.
Missing populations
Which groups were under-represented in the studies has not been recorded.
Why it matters. Recorded by the evidence model as a gap on this record.
What would answer it
A study that measures it, and a reviewer to sign it off.
Last checked 2026-09-04. Searched: The sources listed in the receipts at the foot of this page.
Missing long-term data
No completed tested study window is recorded.
Why it matters. Recorded by the evidence model as a gap on this record.
What would answer it
A study that measures it, and a reviewer to sign it off.
Last checked 2026-09-04. Searched: The sources listed in the receipts at the foot of this page.
No reviewed conclusion
RNAWiki has not yet published a reviewed conclusion for this use.
Why it matters. Recorded by the evidence model as a gap on this record.
What would answer it
A study that measures it, and a reviewer to sign it off.
Last checked 2026-09-04. Searched: The sources listed in the receipts at the foot of this page.
Missing interaction studies
No interaction was found in the registers checked. Not finding one is not the same as showing there is none.
Why it matters. Recorded by the evidence model as a gap on this record.
What would answer it
A study that measures it, and a reviewer to sign it off.
Last checked 2026-09-04. Searched: The sources listed in the receipts at the foot of this page.
Formulation uncertainty
Several salts, forms or products of Givosiran 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.
ENVISION: annualised attack rate 3.2 versus 12.5 on placebo
In plain words
Patients on givosiran had roughly a quarter as many attacks needing hospital care, urgent visits or intravenous haemin.
What was measured
Annualised rate of composite porphyria attacks (hospitalisation, urgent visit or home intravenous haemin)
Effect estimate
No reviewed effect estimate exists for this record.
Limits
See the technical detail.
From the source
Double-blind, placebo-controlled phase 3. 94 patients randomised, 48 to givosiran 2.5 mg/kg monthly and 46 to placebo, for 6 months. Among the 89 patients with acute intermittent porphyria the mean annualised composite attack rate was 3.2 with givosiran and 12.5 with placebo, a 74% lower rate (P<0.001). Urinary aminolevulinic acid and porphobilinogen fell, haemin use fell and daily worst-pain scores improved.
Written into the record, not signed off as a reviewed claim
The efficacy came with more hepatic and renal adverse events
In plain words
Liver enzymes rose, kidney measurements moved, and injection sites reacted more often on the drug than on placebo. The paper says so in its own conclusion.
What was measured
Not recorded
Effect estimate
No reviewed effect estimate exists for this record.
Limits
See the technical detail.
From the source
ENVISION reported that key adverse events observed more frequently with givosiran were elevations in serum aminotransferases, changes in serum creatinine and estimated glomerular filtration rate, and injection-site reactions, and the authors wrote that "the increased efficacy was accompanied by a higher frequency of hepatic and renal adverse events". The FDA label carries warnings for anaphylaxis, hepatic toxicity with scheduled liver testing, renal toxicity, injection-site reactions including recall reactions, increased blood homocysteine and pancreatitis. Nausea and injection-site reactions each occur in at least 20% of patients.
Written into the record, not signed off as a reviewed claim
Six months of attack data are not evidence about the long-term complications
In plain words
The trial ran half a year and counted attacks. It did not measure whether kidney function, nerve damage or liver cancer risk change over the years people will actually take this drug.
What was measured
That fewer attacks over six months means fewer long-term hepatic, renal and neurological complications
Effect estimate
No reviewed effect estimate exists for this record.
Limits
See the technical detail.
From the source
ENVISION's randomised period was 6 months with a primary endpoint of annualised attack rate in 89 patients. Chronic kidney disease progression, established neuropathy, and the elevated hepatocellular carcinoma risk associated with acute hepatic porphyria were not endpoints. The homocysteine elevation named in the label has no established clinical consequence in this population and no trial has tested treating it.
Written into the record, not signed off as a reviewed claim
The attack endpoint is defined by healthcare use, not by a biomarker
In plain words
An "attack" in this trial meant a hospital admission, an urgent care visit, or haemin given at home. That is a real-world definition, and it depends on how easy those things are to reach.
What was measured
Composite attack count as defined by healthcare utilisation
Effect estimate
No reviewed effect estimate exists for this record.
Limits
See the technical detail.
From the source
The composite primary endpoint counted events resulting in hospitalisation, an urgent healthcare visit, or intravenous haemin administration at home. This grounds the endpoint in consequences patients feel, but it also makes it partly a measure of healthcare access and physician threshold, which differ between sites and countries. The biochemical endpoints — urinary aminolevulinic acid and porphobilinogen — were secondary.
Written into the record, not signed off as a reviewed claim
Givosiran is the one approved siRNA that cuts inside the coding sequence
In plain words
Every other approved siRNA aims at the untranslated tail of its target message. Givosiran aims at the protein-coding body of ALAS1 instead.
What was measured
Not recorded
Effect estimate
No reviewed effect estimate exists for this record.
Limits
See the technical detail.
From the source
A 2024 review of the approved RNAi therapeutics notes that givosiran targets the coding sequence of ALAS1 mRNA with near-complete binding, while patisiran, lumasiran, inclisiran, vutrisiran and nedosiran all act on the 3' untranslated regions of their targets. The design consequence is that the guide must tolerate the sequence constraints of a coding region, where synonymous variation is limited.
This order is fixed in code and does not count clicks or time on the page.
What is not here
7 questions this page could not answer
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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.
Silences the first enzyme of haem synthesis so the toxic intermediates stop accumulating, cutting the annualised porphyria attack rate from 12.5 to 3.2 in ENVISION — a 74% reduction bought at the cost of more liver and kidney adverse events.
Recorded evidence blocks (8)
Q1
On the Givosiran label: indicated for what?
"GIVLAARI is indicated for the treatment of adults with acute hepatic porphyria (AHP). GIVLAARI is an aminolevulinate synthase 1-directed small interfering RNA indicated for the treatment of adults with acute hepatic porphyria (AHP).": indications and usage on Givosiran's label. DailyMed label · 167e663c-11e1-497b-a3fc-951d65d58eaa · 2025-09-10
Q2
5 registered trials of Givosiran — at which phases?
Givosiran's half-life is 6 hours — which schedules were studied?
6 hours, the half-life Givosiran's label states: "Elimination Half-Life [Mean (CV%)] 6 hours (46%) 6 hours (41%) Apparent Clearance [Mean (CV%)] 35.1 L/hr (18%) 64.7 L/hr (33%) Metabolism Primary Pathway Givosiran is metabolized by nucleases to oligonucleotides of shorter lengths." DailyMed label · 167e663c-11e1-497b-a3fc-951d65d58eaa · 2025-09-10
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half lifepharmacokinetics
6 hours; Elimination Half-Life [Mean (CV%)] 6 hours (46%) 6 hours (41%) Apparent Clearance [Mean (CV%)] 35.1 L/hr (18%) 64.7 L/hr (33%) Metabolism Primary Pathway Givosiran is metabolized by nucleases to oligonucleotides of shorter lengths.
metabolismpharmacokinetics
Elimination Half-Life [Mean (CV%)] 6 hours (46%) 6 hours (41%) Apparent Clearance [Mean (CV%)] 35.1 L/hr (18%) 64.7 L/hr (33%) Metabolism Primary Pathway Givosiran is metabolized by nucleases to oligonucleotides of shorter lengths.
recorded 2025-09-10 · last checked 2026-09-04
Q4
Which 2 trials of Givosiran posted no result?
Posted no result
2 of 2 completed trials
Registrations
NCT02452372 and NCT03505853
Completion dates
oldest 2017-09-06; newest 2019-01-10
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Trial
NCT02452372
2017-09-06
NCT03505853
2019-01-10
Q5
At the median, Givosiran's trials enrolled 28 people — anything larger?
Median enrolment
28
Largest enrolment
94
Registered trials counted
4
Q6
What do 42 spontaneous reports say about Givosiran — 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.
Givosiran appears in spontaneous reports to regulators. Across the 7 most-reported reaction terms, 42 reaction mentions were counted: porphyria acute 19; blood homocysteine increased 9; hospitalisation 8; hyperhomocysteinaemia 3. FAERS via Open Targets · CHEMBL4594265 · 2026-06-24
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porphyria acute
19
blood homocysteine increased
9
hospitalisation
8
hyperhomocysteinaemia
3
fasting
1
sleep study abnormal
1
1 more recorded row
vitamin b6 decreased
1
recorded 2026-06-24 · last checked 2026-09-04
Q7
Which 7 reactions does Givosiran's label not list?
Sensitive CYP1A2 and CYP2D6 Substrates: Avoid concomitant use with CYP1A2 and CYP2D6 substrates for which minimal concentration changes may lead to serious or life-threatening toxicities.
drug_interactions
( 7.1 ) 7.1 Effect of GIVLAARI on Other Drugs Sensitive CYP1A2 and CYP2D6 Substrates Concomitant use of GIVLAARI increases the concentration of CYP1A2 or CYP2D6 substrates [see Clinical Pharmacology (12.3) ] , which may increase adverse reactions of these substrates.
drug_interactions
Avoid concomitant use of GIVLAARI with CYP1A2 or CYP2D6 substrates, for which minimal concentration changes may lead to serious or life-threatening toxicities.
drug_interactions
If concomitant use is unavoidable, decrease the CYP1A2 or CYP2D6 substrate dosage in accordance with approved product labeling.
pharmacokinetics
Drug Interaction Studies Clinical Studies Effect of givosiran on CYP1A2 Substrates: Concomitant use of a single subcutaneous dose of givosiran 2.5 mg/kg increased caffeine (sensitive CYP1A2 substrate) AUC by 3.1-fold and C max by 1.3-fold [see Drug Interactions (7.1) ] .
pharmacokinetics
Effect of givosiran on CYP2D6 Substrates: Concomitant use of a single subcutaneous dose of givosiran 2.5 mg/kg increased dextromethorphan (sensitive CYP2D6 substrate) AUC by 2.4-fold and C max by 2.0-fold [see Drug Interactions (7.1) ] .
2 more recorded rows
Interaction statementpharmacokinetics
Effect of givosiran on other CYP450 Substrates: Concomitant use of a single subcutaneous dose of givosiran 2.5 mg/kg increased losartan (CYP2C9 substrate) AUC by 1.1-fold with no change in C max ; increased omeprazole (sensitive CYP2C19 substrate) AUC by 1.6-fold and C max by 1.1-fold; increased midazolam (sensitive CYP3A4 substrate) AUC by 1.5-fold and C max by 1.2-fold.
Interaction statementclinical_pharmacology
Drug Interaction Studies Clinical Studies Effect of givosiran on CYP1A2 Substrates: Concomitant use of a single subcutaneous dose of givosiran 2.5 mg/kg increased caffeine (sensitive CYP1A2 substrate) AUC by 3.1-fold and C max by 1.3-fold [see Drug Interactions (7.1) ] .
ChEMBL ATC CC BY-SA · ClinicalTrials.gov — US Government work · Open Targets 26.06 — CC0 · mixed register set; per-register licences in docs/specs/corpus-20k-sources.md · openFDA / DailyMed — US Government work
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