This page shows what was measured, who it was measured in, and what that does not settle.
What Pibrentasvir does in the body
Long-standing hepatitis C infection across all six genetic forms.
Hepatitis C cannot copy itself out in the open. It first folds the liver cell’s own internal membranes into a private workshop, and one viral protein, NS5A, is what holds that workshop together and passes finished copies to the packing line. Pibrentasvir sticks to NS5A in vanishingly small amounts and stops it doing either job, so the workshop never assembles and no virus is packed. It is always given fixed together with a second drug that attacks a different viral protein, because hitting one target alone lets the virus escape.
What happened in people
In a fixed combination, it cured about 98 to 100 in 100 people across major studied groups.
✓ 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
It was never tested alone in an approval study, so its individual contribution is inferred.
Where it acts
Hepatocyte cytoplasm — the membranous web of remodelled endoplasmic reticulum where NS5A holds the replication complex together
Kind of result
The kind of result is not recorded
Supervision
RNAWiki has not recorded a supervision or regulatory status for this substance.
What the registries record it as
The substance registry classes this as chemical.
FDA substance registry · 2WU922TK3L · read 2026-08-29
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 118 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.
Comparator
A comparator is whatever the treatment was measured against.
A picture of it, and where the picture fails
It is like the other runner in a race.
Where that stops being true. A race has one winner. A study can show both arms improved.
What people get wrong. Results are read without asking what the other group got. Beating nothing is not beating a treatment.
The control condition against which the experimental intervention is assessed.
Randomisation
Randomisation means chance decides who gets which treatment.
A picture of it, and where the picture fails
It is like a coin toss deciding the groups.
Where that stops being true. A coin toss is fair once. Fairness here comes from doing it for everyone.
What people get wrong. It is thought to make groups identical. It makes them similar on average, including on things nobody measured.
Allocation of participants to arms by a chance process, so that unmeasured factors are balanced in expectation.
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.
Sustained virologic response 12 weeks after end of treatment, genotype 2
97.7% (335/343; 95% CI 96.1 to 99.3) by intention to treat; 99.7% (334/335; 95% CI 98.3 to 99.9) per protocol
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. Single-arm, so the 2% serious adverse event rate in a cirrhotic population has no concurrent comparator. The comparison that established the 8-week duration was against historical 12-week rates, not a randomised control.
How far it carries. This study is recorded from the curated record, not from the registry match.
Form and route. Oral fixed-dose combination tablet with glecaprevir, and oral pellets for children
Interval reported. 95% CI 96
Written into the record, not signed off as a reviewed claim.
89% (39/44) at 12 weeks and 91% (43/47) at 16 weeks
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. Prior failure of both a protease inhibitor and an NS5A inhibitor was associated with a lower SVR12 rate; that subgroup is excluded from the approved retreatment indication.
How far it carries. This study is recorded from the curated record, not from the registry match.
Form and route. Oral fixed-dose combination tablet with glecaprevir, and oral pellets for children
Interval reported. Not recorded in this summary
Written into the record, not signed off as a reviewed claim.
Sustained virologic response 12 weeks after end of treatment, genotype 3
✓ The study showed what it set out to show
Who was studied
SURVEYOR-II Part 3 (NCT02243293)
How many people
131
Study design
Phase 3, partially randomised, open-label, genotype 3 with cirrhosis or prior treatment
Compared against
Not recorded for this study
Kind of result
A number that stands in for health
What was found
91% (20/22) at 12 weeks and 95% (21/22) at 16 weeks in treatment-experienced patients without cirrhosis; 98% (39/40) in treatment-naive cirrhosis at 12 weeks; 96% (45/47) in treatment-experienced cirrhosis at 16 weeks
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. Only the treatment-experienced non-cirrhotic patients were randomised; the two cirrhotic groups were assigned by prior treatment status, so duration and population are confounded.
How far it carries. This study is recorded from the curated record, not from the registry match.
Form and route. Oral fixed-dose combination tablet with glecaprevir, and oral pellets for children
Interval reported. Not recorded in this summary
Written into the record, not signed off as a reviewed claim.
RNAWiki holds 4 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
Pibrentasvir
What a person takes: Oral fixed-dose combination tablet with glecaprevir, and oral pellets for children.
The measurement behind this step
Three tablets once daily with food; absorption falls substantially when taken fasting. Pibrentasvir is not sold separately and has no single-agent presentation. Pellets exist for children from age 3.
Getting in
Swallowed fixed to a second drug, with food
Pibrentasvir is not sold on its own. It is pressed into the same tablet as glecaprevir, and the tablets are taken with food because absorption is much lower on an empty stomach.
╌╌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
Fixed-dose combination of 40 mg pibrentasvir with 100 mg glecaprevir per tablet, three tablets once daily; oral pellets exist for children from age 3. Both components are substrates and inhibitors of P-glycoprotein and BCRP.
Transporters on the liver-cell surface draw the drug in, and it leaves the body in bile rather than urine. Almost none of it is cleared by the kidney.
╌╌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
Hepatic uptake with biliary elimination and negligible renal clearance, which is why the combination is usable across the full range of kidney function including dialysis. Unlike glecaprevir, pibrentasvir exposure is not meaningfully reduced by high-dose proton pump inhibitors.
It binds NS5A, the protein that has no job you can point at
NS5A does not cut or copy anything. It organises: it holds the viral workshop together and hands finished genomes to the packing line. Pibrentasvir sticks to it in trillionths of a gram.
╌╌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
Binds the NS5A phosphoprotein with median replicon EC50 of 0.5 to 15.6 pM across thirteen subtypes. NS5A has no catalytic site, so the binding surface is a protein-protein interface at domain I rather than an enzyme pocket — the reason this class was not obvious to look for and the reason its potency was a surprise.
The replication workshop never forms and nothing gets packed
Two things stop at once: the membrane compartment where the virus copies itself is never properly built, and the genomes already made are never loaded into new particles.
╌╌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
NS5A is required both for viral RNA replication on the membranous web and for virion assembly through its domain III interaction with core protein. Inhibiting it collapses replication complex formation and blocks assembly, which is why NS5A inhibitors clear viral RNA from serum faster in the first days of treatment than any other class.
Eight weeks is the standard course for most previously untreated people, including those who already have a scarred liver.
──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
SVR12 was 99.5% at 12 weeks in genotype 2 against a placebo arm, 98% at 8 weeks in genotype 2 and 93% at 8 weeks in genotypes 4, 5 and 6 without cirrhosis, and 97.7% by intention to treat at 8 weeks in 343 treatment-naive patients with compensated cirrhosis across genotypes 1 to 6.
Where it stops working is a subtype, not a genotype
Genotype 3b carries natural changes that blunt the drug from the outset, and one further change makes it thousands of times weaker. Genotype 3 accounted for twenty of the twenty-four failures in the whole approval programme.
╌╌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
Natural K30 and M31 in genotype 3b NS5A cost 24-fold against genotype 3a; adding Y93H costs 6,336-fold. A genotype 1b P32 deletion costs 1,036-fold. Of the 24 registrational virologic failures, 20 were genotype 3 and none were genotype 4, 5 or 6.
No suggested links are held for this record, so nothing is hidden from this path.
What we know
The record describes 6 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 and children aged 3 and over with any of the six genotypes. It is never taken alone: it is only sold fixed together with glecaprevir, because a single direct-acting antiviral selects resistance.
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
Genotype 3b carries natural NS5A polymorphisms that blunt the drug before treatment starts, and a Y93H addition costs a further 6,336-fold
A genotype 1b NS5A P32 deletion costs 1,036-fold, and genotype 1a M28G and Q30D cost 244-fold and 94-fold
Twenty of the 24 registrational virologic failures were genotype 3; two genotype 2 failures had no treatment-emergent substitution at all
Retreatment after failure of both a protease inhibitor and an NS5A inhibitor performed worst and is excluded from the label; 13 of 177 failed again in the sofosbuvir plus NS5A retreatment study
Adding ribavirin to retreatment increased adverse events without increasing efficacy
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
Prescription only
❝ 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
Oral fixed-dose combination tablet with glecaprevir, and oral pellets for children
✎ 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
RNAWiki has not recorded a supervision or regulatory status for this substance.
❝ Quoted from a source
Where this came from
Copied from a source RNAWiki stored, with the source named.
No register row and no identity class settled the question.
No source is stored against this line.
What is in the pack
Three tablets once daily with food; absorption falls substantially when taken fasting. Pibrentasvir is not sold separately and has no single-agent presentation. Pellets exist for children from age 3.
✎ 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
In ENDURANCE-2, the only placebo-controlled arm in the programme, adverse event frequency and severity on treatment were similar to placebo. In EXPEDITION-8 the commonest events were fatigue (9%), pruritus (8%), headache (8%) and nausea (6%); serious adverse events occurred in 2%, none assessed as related, and none led to discontinuation. In MAGELLAN-1 Part 2 the only adverse event reported in at least 10% was headache, with no drug-related serious events. The contraindications carried by the tablet — Child-Pugh B or C hepatic impairment, prior hepatic decompensation, atazanavir and rifampin — arise from glecaprevir, not from pibrentasvir. A boxed warning for hepatitis B virus reactivation applies to the class.
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◇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
Oral fixed-dose combination tablet with glecaprevir, and oral pellets for children
✎ 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
Pibrentasvir is not sold separately and has no single-agent presentation. Pellets exist for children from age 3.
✎ 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. 1 of them contain it and nothing else.
FDA National Drug Code directory · 68543-2625 · read 2026-08-29
They are sold as pellet and tablet, film coated, taken oral.
FDA National Drug Code directory · 68543-2625 · read 2026-08-29
1 published label names it as an active ingredient. None of them describes this substance alone, so no label text on this page can be attributed to it rather than to a combination.
US prescribing information · 7bf99777-0401-9095-8645-16c6e907fcc0 · read 2026-08-29
Those labels are classed as human prescription drug.
US prescribing information · 7bf99777-0401-9095-8645-16c6e907fcc0 · read 2026-08-29
Mavyret is oral at 3 DOSAGE FORMS AND STRENGTHS MAVYRET is available as tablets or pellets for oral use., recorded as fda label in effect 2025-06-25 in the United States.
US prescribing information · 7bf99777-0401-9095-8645-16c6e907fcc0 · 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.
RNAWiki could not confidently classify this substance, so no self-experiment plan is offered.
Questions worth asking
Which of the trials of Pibrentasvir 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 any cure rate here measures pibrentasvir — every registrational arm tested the fixed two-drug combination and none isolated it
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 "pan-genotypic" means uniform potency: the replicon range spans 31-fold across subtypes before any resistance substitution is added
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 an 8-week course in cirrhosis was shown non-inferior to 12 weeks — EXPEDITION-8 was single-arm against pre-defined historical thresholds
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 clearing virus from the blood of a cirrhotic patient has been shown to reduce cancers, transplants or deaths; that outcome was not measured
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 Pibrentasvir 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.
ENDURANCE-2: a direct-acting antiviral trial that actually used a placebo
In plain words
Almost no modern hepatitis C trial has a placebo group, because withholding a cure is hard to justify. This one did, for twelve weeks, in genotype 2. Nearly everyone on the drug was cured and the side effect rate was no different from placebo.
What was measured
Sustained virologic response at 12 weeks, against a concurrent double-blind placebo arm
Effect estimate
No reviewed effect estimate exists for this record.
Limits
See the technical detail.
From the source
ENDURANCE-2 randomised adults with untreated or previously treated genotype 2 infection without cirrhosis 2:1 to once-daily glecaprevir 300 mg with pibrentasvir 120 mg (n = 202) or placebo (n = 100) for 12 weeks, double-blind. SVR12 in the intention-to-treat population was 99.5% (95% CI 98.5 to 100). The frequency and severity of adverse events on active treatment were similar to placebo, which is the specific claim a single-arm trial cannot make and this one can.
Written into the record, not signed off as a reviewed claim
EXPEDITION-8: eight weeks worked in 343 patients who already had cirrhosis
In plain words
Cirrhosis had always meant longer treatment. This trial gave the eight-week course to 343 previously untreated people who already had scarred livers. One person relapsed.
What was measured
Sustained virologic response at 12 weeks after an 8-week course in compensated cirrhosis
Effect estimate
No reviewed effect estimate exists for this record.
Limits
See the technical detail.
From the source
EXPEDITION-8 was a single-arm, multicentre phase 3b trial of 8 weeks of glecaprevir/pibrentasvir in treatment-naive patients with genotypes 1 to 6 and compensated cirrhosis. SVR12 was 99.7% (334 of 335; 95% CI 98.3 to 99.9) per protocol and 97.7% (335 of 343; 95% CI 96.1 to 99.3) by intention to treat. One patient, genotype 3a, relapsed at post-treatment week 4. Serious adverse events occurred in 2% and none were assessed as related; no adverse event led to discontinuation. The gap between the two figures is the eight patients who did not complete per-protocol follow-up, not eight treatment failures.
Written into the record, not signed off as a reviewed claim
Picomolar potency across thirteen subtypes, which is not a marketing adjective
In plain words
The concentration needed to halve viral copying is measured in trillionths of a gram per litre. Its partner drug needs about a thousand times more. NS5A inhibitors are the most potent antivirals anyone has measured.
What was measured
Median replicon EC50 by viral subtype
Effect estimate
No reviewed effect estimate exists for this record.
Limits
See the technical detail.
From the source
In HCV replicon assays pibrentasvir had median EC50 values of 0.5 to 15.6 pM against laboratory and clinical isolates from subtypes 1a, 1b, 2a, 2b, 3a, 3b, 4a, 4b, 4d, 5a, 6a, 6e and 6p. Glecaprevir over an overlapping panel was 0.08 to 4.6 nM. The range within the pibrentasvir panel is itself 31-fold, so "pan-genotypic" describes clinical adequacy across the panel, not equal potency across it.
Source
MAVYRET United States prescribing information, Microbiology 12.4, antiviral activity (NDA 209394)
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
Genotype 3b: the subtype where the pan-genotypic claim measurably breaks
In plain words
One subtype of genotype 3 carries two natural changes that blunt the drug before treatment starts, and a third change makes it more than six thousand times weaker. This is not a rare escape mutant — the first two changes are ordinary features of that subtype.
What was measured
Fold-change in pibrentasvir susceptibility on a genotype 3b background: 24-fold from natural K30 and M31, 6,336-fold with Y93H added
Effect estimate
No reviewed effect estimate exists for this record.
Limits
This entry records a failure.
From the source
In a genotype 3b replicon the naturally occurring NS5A polymorphisms K30 and M31 reduced pibrentasvir susceptibility 24-fold relative to its activity in a genotype 3a replicon. Introducing NS5A Y93H into that genotype 3b background reduced susceptibility a further 6,336-fold. A genotype 1b P32 deletion cost 1,036-fold, and in genotype 1a, M28G cost 244-fold and Q30D 94-fold. Subtype 3b is uncommon in North America and western Europe and substantially more common in parts of South, Southeast and East Asia, so the registrational population under-represents the subtype in which the drug is weakest.
Source
MAVYRET United States prescribing information, Microbiology 12.4, resistance in cell culture (NDA 209394)
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
Retreatment after both drug classes was the worst arm in its own trial
In plain words
For people whose earlier treatment failed, this combination worked well if they had been exposed to one class of hepatitis C drug. Those exposed to both classes did worse, and the label now excludes them.
What was measured
SVR12 by number of prior direct-acting antiviral classes failed, and the resulting label restriction
Effect estimate
No reviewed effect estimate exists for this record.
Limits
This entry records a failure.
From the source
MAGELLAN-1 Part 2 randomised 91 treated patients with past virologic failure on at least one NS3/4A protease or NS5A inhibitor regimen to 12 or 16 weeks of ribavirin-free glecaprevir/pibrentasvir. SVR12 was 89% (39 of 44) at 12 weeks and 91% (43 of 47) at 16 weeks; relapse occurred in 9% (4 of 44) at 12 weeks and in none at 16 weeks. Past treatment with one class had no impact on SVR12, whereas past treatment with both classes was associated with a lower SVR12 rate. The approved retreatment indication is correspondingly restricted to genotype 1 patients previously treated with an NS5A inhibitor or a protease inhibitor, but not both.
Written into the record, not signed off as a reviewed claim
One in fourteen failed again after a previous sofosbuvir plus NS5A regimen
In plain words
A separate trial retreated 177 people whose earlier sofosbuvir-plus-NS5A course had failed. Thirteen failed a second time. Adding ribavirin caused more side effects and did not raise the cure rate.
What was measured
SVR12 on retreatment after sofosbuvir plus an NS5A inhibitor failure
Effect estimate
No reviewed effect estimate exists for this record.
Limits
This entry records a failure.
From the source
This phase 3b open-label study randomised 177 genotype 1 patients with prior failure on sofosbuvir plus an NS5A inhibitor: without cirrhosis to 12 weeks (n = 78) or 16 weeks (n = 49), and with compensated cirrhosis to 12 weeks with ribavirin (n = 21) or 16 weeks without (n = 29). SVR12 was 90%, 94%, 86% and 97% across the four groups. Treatment failed in 13 patients (7.3%), all genotype 1a. Most patients had baseline NS5A resistance-associated substitutions; treatment-emergent substitutions appeared in NS3 in 9 and in NS5A in 10 of those who failed. Ribavirin increased adverse events without increasing efficacy.
Written into the record, not signed off as a reviewed claim
No number on this page belongs to pibrentasvir alone
In plain words
Every cure rate quoted here comes from a fixed tablet containing two drugs. Pibrentasvir has never been given by itself in a registrational trial, so its individual contribution to the result is inferred, not measured.
What was measured
That the trial cure rates measure pibrentasvir’s efficacy — they measure a two-drug fixed combination, and no arm separated the two
Effect estimate
No reviewed effect estimate exists for this record.
Limits
See the technical detail.
From the source
Pibrentasvir is not marketed separately and was not studied as monotherapy in the registrational programme; the ENDURANCE, EXPEDITION, SURVEYOR and MAGELLAN trials all tested the fixed combination. What is measured separately is the biochemistry: replicon EC50 by subtype, resistance selection, and the observation that combining the two showed no antagonism in genotype 1 replicon assays. The clinical attribution — that the picomolar potency is what buys the eight-week duration — is a mechanistic inference consistent with the data rather than a finding from a trial that isolated it.
Source
MAVYRET United States prescribing information, Microbiology 12.4, combination antiviral activity (NDA 209394)
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
Every endpoint is a blood test twelve weeks after the last tablet
In plain words
The trials counted whether virus was still detectable in blood. None of them counted deaths, liver cancers or transplants.
What was measured
That an undetectable blood test at twelve weeks in a cirrhotic patient predicts fewer cancers, transplants or deaths — plausible, and not what these trials measured
Effect estimate
No reviewed effect estimate exists for this record.
Limits
See the technical detail.
From the source
The 2017 Cochrane review of 138 randomised direct-acting antiviral trials in 25,232 participants found no usable randomised evidence on hepatitis C-related morbidity or on hepatocellular carcinoma, and mortality data from only 11 trials. EXPEDITION-8 is where the gap is most visible in this programme: it enrolled the patients with the most to lose — 343 with established cirrhosis — was single-arm, and stopped measuring twelve weeks after the last dose.
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What is not here
7 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.
What changed on this page — found nothing in the sources checked.
The record as stored
The full record, for auditing
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The older medicine-wide conclusion held in this record
Written for a clinical reader, and about the medicine as a whole rather than about one indication, population and set of trials. RNAWiki does not treat it as a programme conclusion and no reviewer has signed it off in that form. It is here word for word because it is what the record holds.
An NS5A inhibitor of extraordinary potency — median replicon EC50 of 0.5 to 15.6 picomolar across thirteen viral subtypes, roughly a thousandfold below its own protease-inhibitor partner — which cured 99.5% of genotype 2 patients in the rare placebo-controlled ENDURANCE-2 and 97.7% of 343 previously untreated patients with compensated cirrhosis in eight weeks in EXPEDITION-8, and which loses 6,336-fold of that potency against a genotype 3b virus carrying a single Y93H change.
Recorded evidence blocks (6)
Q1
52 registered trials of Pibrentasvir — at which phases?
Registered studies posting no result
16 of 52
52 registered studies of Pibrentasvir: 28 phase3, 13 phase2, 8 phase4, 5 na or unstated, 3 phase1, 2 na, 1 early phase1. CLINICALTRIALS_SNAPSHOT · 2026-09-01
61 with a PubMed record
Show the evidence
phase3
28
phase2
13
phase4
8
na or unstated
5
phase1
3
na
2
8 more recorded rows
early phase1
1
completed
41
unknown
4
recruiting
2
terminated
2
active not recruiting
1
approved for marketing
1
withdrawn
1
recorded 2026-09-01 · last checked 2026-09-04
Q2
3 of Pibrentasvir's trials stopped: accrual/recruitment, funding/business, other?
NCT02296905, NCT02442258, NCT04047680, NCT03492112, NCT05108935 and NCT04682509, and 1 more
Completion dates
oldest 2015-09; newest 2024-04-15
Show the evidence
Trial
NCT02296905
2015-09
NCT02442258
2015-12
NCT04047680
2019-06
NCT03492112
2021-11-30
NCT05108935
2023-03-30
NCT04682509
2024-02-28
1 further recorded trialNCT05446857
2024-04-15
Q5
At the median, Pibrentasvir's trials enrolled 101 people — anything larger?
Median enrolment
101
Largest enrolment
800
Registered trials counted
51
Q6
What do 4027 spontaneous reports say about Pibrentasvir — 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.
Pibrentasvir appears in spontaneous reports to regulators. Across the 6 most-reported reaction terms, 4027 reaction mentions were counted: fatigue 1515; headache 1384; nausea 675; pruritus 414. FAERS via Open Targets · CHEMBL3545123 · 2026-06-24
Show the evidence
fatigue
1515
headache
1384
nausea
675
pruritus
414
viral load increased
28
drug hypersensitivity
11
recorded 2026-06-24 · last checked 2026-09-04
Where it is registeredIdentifiers, relations and other names
ChEMBL 37 — CC BY-SA 3.0 Unported · ClinicalTrials.gov — US Government work · Open Targets 26.06 — CC0 · mixed register set; per-register licences in docs/specs/corpus-20k-sources.md
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✓ source coverage passed: 5 source rows
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