This page shows what was measured, who it was measured in, and what that does not settle.
What Sofosbuvir does in the body
Hepatitis C copies its genetic material with an enzyme that strings building blocks together.
Sofosbuvir is swallowed as an inert form that liver cells strip down into a counterfeit building block. The viral enzyme cannot tell the difference, picks it up, adds it to the growing chain, and then finds it has nothing to attach the next piece to. Copying stops, and because human enzymes do not accept the counterfeit, healthy cells carry on unaffected.
Why people take it. Long-standing hepatitis C infection.
What happened in people
Modern combinations cured about 8 to 9 in 10 treated people.
✓ 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 measured virus clearance, not deaths, liver cancer or transplants over long follow-up.
Where it acts
Hepatocyte cytoplasm — the viral replication complex on remodelled endoplasmic reticulum membrane
Kind of result
The kind of result is not recorded
Supervision
Professional supervision is normally required. A regulator classifies this substance in a way that restricts how it is supplied.
What the registries record it as
The substance registry classes this as chemical.
FDA substance registry · WJ6CA3ZU8B · read 2026-08-29
Its recorded molecular formula is C22H29FN3O9P, weighing 529.45.
US prescribing information · 80beab2c-396e-4a37-a4dc-40fdb62859cf · read 2026-08-30
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 90 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 therapy
✓ The study showed what it set out to show
Who was studied
POSITRON (NCT01542788)
How many people
278
Study design
Phase 3, randomised, placebo-controlled
Compared against
A dummy treatment
Kind of result
A number that stands in for health
What was found
P < 0.001 for 78% (95% CI 72 to 83) against 0% on placebo
Repeated elsewhere
Replicated
What this does not prove. Meeting one endpoint in one population does not carry to other goals or other people.
The limits of this study, and where it came from
Main limit. No limitation is recorded for this study.
How far it carries. This study is recorded from the curated record, not from the registry match.
Form and route. Oral tablet (200 mg and 400 mg) and oral pellets for children
Interval reported. 95% CI 72 to 83) against 0% on placebo
Written into the record, not signed off as a reviewed claim.
Sustained virologic response 12 weeks after end of therapy
✓ The study showed what it set out to show
Who was studied
NEUTRINO (NCT01641640)
How many people
327
Study design
Phase 3, single-group, open-label
Compared against
Not recorded for this study
Kind of result
A number that stands in for health
What was found
90% (95% CI 87 to 93); no concurrent control arm, historical comparison
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. Single-arm design. The 90% figure has no internal comparator, and the regimen included peginterferon and ribavirin, so it is not a measurement of sofosbuvir alone.
How far it carries. This study is recorded from the curated record, not from the registry match.
Form and route. Oral tablet (200 mg and 400 mg) and oral pellets for children
Interval reported. 95% CI 87 to 93); no concurrent control arm, historical comparison
Written into the record, not signed off as a reviewed claim.
67% in both arms; noninferiority met, superiority not shown. Genotype 3 56% against genotype 2 97% within the sofosbuvir arm.
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. The genotype 3 result is in the abstract but is easily lost behind the headline 67%. Genotype 3 was the population sofosbuvir-ribavirin served worst.
How far it carries. This study is recorded from the curated record, not from the registry match.
Form and route. Oral tablet (200 mg and 400 mg) 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 therapy
✓ The study showed what it set out to show
Who was studied
VALENCE (NCT01682720)
How many people
419
Study design
Phase 3, randomised then unblinded and redesigned mid-study
Compared against
Not recorded for this study
Kind of result
A number that stands in for health
What was found
Genotype 2 at 12 weeks 93% (95% CI 85 to 98); genotype 3 at 24 weeks 85% (95% CI 80 to 89). Descriptive only after unblinding.
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. The placebo group was terminated and hypothesis testing abandoned partway through, on the strength of emerging FUSION data. The result is therefore descriptive, and the paper says so.
How far it carries. This study is recorded from the curated record, not from the registry match.
Form and route. Oral tablet (200 mg and 400 mg) and oral pellets for children
Interval reported. 95% CI 85 to 98); genotype 3 at 24 weeks 85% (95% CI 80 to 89)
Written into the record, not signed off as a reviewed claim.
RNAWiki holds 5 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
Sofosbuvir
What a person takes: Oral tablet (200 mg and 400 mg) and oral pellets for children.
The measurement behind this step
Taken once daily with or without food; a high-fat meal does not meaningfully change exposure. Pellets exist so the drug can be given to children from age 3, which is why the paediatric indication could be written at all.
Getting in
Swallowed as a disguised molecule
The tablet contains a version of the drug wrapped in a chemical disguise. The disguise does nothing against the virus. Its only job is to let the molecule get inside a liver cell, which the working form could never do on its own.
──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
Sofosbuvir is a phosphoramidate ProTide: an isopropyl alanine ester and a phenol group mask the negatively charged 5-monophosphate. Peak plasma concentration comes at roughly 0.5 to 2 hours, unaffected by a high-fat meal, with 61 to 65% plasma protein binding and a median terminal half-life of 0.4 hours for the parent drug.
Once inside a liver cell, three separate enzymes take the wrapping apart one layer at a time. This only happens efficiently inside liver cells, which is why the drug concentrates where the virus lives.
╌╌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
Cathepsin A or carboxylesterase 1 hydrolyses the carboxyl ester; histidine triad nucleotide-binding protein 1 (HINT1) cleaves the phosphoramidate to release the nucleoside monophosphate; cellular pyrimidine kinases add the second and third phosphates to give GS-461203. Dephosphorylation instead yields GS-331007, which cannot be efficiently rephosphorylated and has no antiviral activity; it accounts for more than 90% of circulating drug-related material and is cleared renally with a 27-hour half-life.
The virus copies its genome and picks up the counterfeit
Hepatitis C copies itself with an enzyme that reads its own genetic code and builds a matching strand. The activated drug looks close enough to a real building block that the enzyme accepts it.
╌╌Described, with no measurement named. No measurement is named for this step, so it is drawn as an unconfirmed link.
The measurement behind this step
GS-461203 is a uridine analog triphosphate. NS5B, the viral RNA-dependent RNA polymerase, incorporates it into the nascent RNA strand. In biochemical assay it inhibits recombinant NS5B from genotypes 1b, 2a, 3a and 4a with IC50 values of 0.7 to 2.6 micromolar, and replicon EC50 values span 0.014 to 0.11 micromolar across genotypes 1a to 6a.
The counterfeit block has no attachment point for the next one. The growing copy is stuck at that position, and the virus cannot finish a genome.
──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
The 2-fluoro-2-methyl substitution on the ribose sterically and electronically blocks the addition of the next nucleotide, making incorporation a non-obligate chain termination. Because GS-461203 inhibits neither human DNA and RNA polymerases nor mitochondrial RNA polymerase, host replication and mitochondrial transcription are unaffected — the structural basis for the drug being essentially free of the toxicity that ended earlier nucleoside programmes.
With copying blocked, infected cells are cleared and no new ones are infected. If blood tests still show no virus twelve weeks after the last tablet, relapse after that point is rare.
╌╌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 endpoint is SVR12: HCV RNA below the lower limit of quantification 12 weeks after end of therapy. Resistance is unusual because the only substitution conferring cross-genotype resistance, S282T, reduces viral replication capacity by 89% to 99% and is outcompeted by wild-type virus.
Clearing the virus is not the same as being shown to live longer. No randomised trial has followed patients long enough to count deaths, cancers or transplants, so that part of the story is inference.
──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 is a virological surrogate accepted by regulators on observational evidence. The 2017 Cochrane review of 138 trials in 25,232 participants found no usable randomised data on hepatitis C-related morbidity, hepatocellular carcinoma, ascites, variceal bleeding or encephalopathy, and only 11 trials reporting any mortality.
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 chronic hepatitis C. It is never given alone: the label requires it as a component of a combination regimen, 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.
What the label states about particular groups
On pediatric, the label states: “SOVALDI was evaluated in an open-label clinical trial (Study 1112), which included 106 subjects (31 genotype 2; 75 genotype 3) 3 years of age and older.”
US prescribing information · 80beab2c-396e-4a37-a4dc-40fdb62859cf · read 2026-08-30
On older people, the label states: “SOVALDI was administered to 90 subjects aged 65 and over.”
US prescribing information · 80beab2c-396e-4a37-a4dc-40fdb62859cf · read 2026-08-30
On people who are pregnant, the label states: “Risk Summary If SOVALDI is administered with ribavirin or peginterferon alfa and ribavirin, the combination regimen is contraindicated in pregnant women and in men whose female partners are pregnant.”
US prescribing information · 80beab2c-396e-4a37-a4dc-40fdb62859cf · read 2026-08-30
On people who are breastfeeding, the label states: “Risk Summary It is not known whether sofosbuvir or its metabolites are present in human breast milk, affect human milk production or have effects on the breastfed infant.”
US prescribing information · 80beab2c-396e-4a37-a4dc-40fdb62859cf · read 2026-08-30
On people with reduced liver function, the label states: “Safety and efficacy of SOVALDI have not been established in patients with decompensated cirrhosis .”
US prescribing information · 80beab2c-396e-4a37-a4dc-40fdb62859cf · read 2026-08-30
On people with reduced kidney function, the label states: “The safety and efficacy of SOVALDI have not been established in patients with severe renal impairment (eGFR less than 30 mL/min/1.73m 2 ) or ESRD requiring hemodialysis.”
US prescribing information · 80beab2c-396e-4a37-a4dc-40fdb62859cf · read 2026-08-30
Where the result stopped carrying
FISSION showed no superiority over the interferon regimen it replaced: 67% in both arms
Genotype 3 responded at 56% against 97% for genotype 2 on sofosbuvir-ribavirin, and cirrhosis dropped genotype 3 to 68% even at 24 weeks
Twelve weeks failed in previously treated patients, curing half of them, and the duration had to be extended
Symptomatic bradycardia with amiodarone, including one fatal cardiac arrest, and hepatitis B reactivation, including deaths, were both found only after approval
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 tablet (200 mg and 400 mg) 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
Professional supervision is normally required. A regulator classifies this substance in a way that restricts how it is supplied.
❝ Quoted from a source
Where this came from
Copied from a source RNAWiki stored, with the source named.
Suppression classes recorded: S6.
No source is stored against this line.
What is in the pack
Taken once daily with or without food; a high-fat meal does not meaningfully change exposure. Pellets exist so the drug can be given to children from age 3, which is why the paediatric indication could be written at all.
✎ Source-linked record
Where this came from
A person wrote this into the record with the study named beside it. No reviewer has signed it off.
Recorded notes on how this is sold and what that means for what is in the pack.
No source is stored against this line.
Where it is registered
Regulatory records are listed in the technical disclosure at the foot of this page.
# Counted from records
Where this came from
A count of rows RNAWiki holds. It describes our records, not your body.
Register entries are stored per jurisdiction and shown with their dates.
No source is stored against this line.
Why people stop
Not recorded.
∅ Nothing recorded
Where this came from
RNAWiki holds nothing here and says so rather than guessing.
No record of why people stopped taking it is stored for this substance.
No source is stored against this line.
What it would be like to take◇Read from sources, not yet reviewed
What can go wrong
Sorted by where each line came from. A regulator's label and a report somebody sent in are not the same kind of fact.
·Worth asking a clinician aboutWritten into the record from the studies named on this page
Boxed warning for hepatitis B virus reactivation in HCV/HBV coinfected patients, including fulminant hepatitis, hepatic failure and death, and including patients whose HBV appeared resolved. Coadministration with amiodarone is not recommended after postmarketing reports of symptomatic bradycardia, pacemaker intervention and one fatal cardiac arrest. Commonest trial adverse events were fatigue, headache, nausea and insomnia; discontinuation for adverse events was 1 to 2%. At three times the maximum dose the drug did not prolong QTc to a clinically relevant extent.
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 tablet (200 mg and 400 mg) 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
Pellets exist so the drug can be given to children from age 3, which is why the paediatric indication could be written at all.
✎ 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
25 products list this as an active ingredient in the United States drug directory. 13 of them contain it and nothing else.
FDA National Drug Code directory · 61958-1801 · read 2026-08-29
They are sold as pellet, powder and tablet, film coated, taken oral.
FDA National Drug Code directory · 61958-1801 · read 2026-08-29
The regulator's established pharmacologic class for it is hepatitis c virus nucleotide analog ns5b polymerase inhibitor [epc] and rna replicase inhibitors [moa].
FDA National Drug Code directory · 61958-1801 · read 2026-08-29
6 published labels name 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 · 7f30631a-ee3b-4cfe-866b-964df3f0a44f · read 2026-08-29
Those labels are classed as human prescription drug.
US prescribing information · 7f30631a-ee3b-4cfe-866b-964df3f0a44f · read 2026-08-29
Sovaldi is oral at 3 DOSAGE FORMS AND STRENGTHS SOVALDI is available as tablets or pellets for oral use., recorded as fda label in effect 2024-12-26 in the United States.
US prescribing information · 80beab2c-396e-4a37-a4dc-40fdb62859cf · 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 Sofosbuvir 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 clearing the virus has been shown in a randomised trial to reduce deaths, liver cancers or transplants — no such 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 launch price reflects manufacturing or development cost, when the same course was listed at US$25,000 in Spain
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 direct-acting antivirals cause liver cancer, an alarm from 2016 that adjustment for age and follow-up time dissolved
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 a cure rate measured with peginterferon and ribavirin in the regimen is a measurement of sofosbuvir on its own
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 Sofosbuvir 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.
POSITRON: 78% cured against 0% on matching placebo
In plain words
This is the cleanest result the drug has. Patients who could not take interferon were randomised to sofosbuvir with ribavirin or to a dummy tablet. Four in five on the drug cleared the virus. Nobody on placebo did.
What was measured
Sustained virologic response 12 weeks after end of therapy, against matching placebo
Effect estimate
No reviewed effect estimate exists for this record.
Limits
See the technical detail.
From the source
In POSITRON, 207 patients with genotype 2 or 3 hepatitis C for whom peginterferon was not an option received sofosbuvir plus ribavirin for 12 weeks and 71 received matching placebo. Sustained virologic response at 12 weeks was 78% (95% CI 72 to 83) on treatment against 0% on placebo, p<0.001. Response was lower in genotype 3 than genotype 2, and lower in cirrhosis than without it. Discontinuation of sofosbuvir for adverse events was 1 to 2%.
Written into the record, not signed off as a reviewed claim
NEUTRINO: 90% cured in 327 previously untreated patients
In plain words
In the trial that supported approval, nine in ten previously untreated patients cleared the virus after twelve weeks. The comparison was against what earlier drugs had achieved, not against a placebo group in the same trial.
What was measured
Sustained virologic response at 12 weeks in a single-arm study
Effect estimate
No reviewed effect estimate exists for this record.
Limits
See the technical detail.
From the source
NEUTRINO was a single-group, open-label study of sofosbuvir plus peginterferon alfa-2a and ribavirin for 12 weeks in 327 previously untreated patients with genotype 1, 4, 5 or 6, of whom 98% had genotype 1 or 4. Sustained virologic response at 12 weeks was 90% (95% CI 87 to 93). There was no concurrent control arm; the trial was designed to be compared against a historical response rate.
Written into the record, not signed off as a reviewed claim
FISSION: identical to the old interferon regimen it was meant to replace
In plain words
In the head-to-head trial against the drug it was replacing, sofosbuvir with ribavirin cured exactly the same proportion — 67% — as twenty-four weeks of interferon. It was better tolerated and shorter. It was not more effective.
What was measured
Sustained virologic response, sofosbuvir-ribavirin against peginterferon-ribavirin
Effect estimate
No reviewed effect estimate exists for this record.
Limits
This entry records a failure.
From the source
FISSION randomised 499 previously untreated patients with genotype 2 or 3 to sofosbuvir plus ribavirin for 12 weeks or peginterferon alfa-2a plus ribavirin for 24 weeks. Sustained virologic response was 67% in both groups. Within the sofosbuvir arm the split was stark: 97% in genotype 2 against 56% in genotype 3. Adverse events including fatigue, headache, nausea and neutropenia were less common with sofosbuvir. The trial met its noninferiority objective and did not show superiority.
Written into the record, not signed off as a reviewed claim
FUSION: half of previously treated patients relapsed at the approved duration
In plain words
Patients who had already failed interferon were given twelve or sixteen weeks of sofosbuvir with ribavirin. Twelve weeks cured half of them. Sixteen weeks cured nearly three-quarters. Duration, not the drug, decided the outcome.
What was measured
Sustained virologic response at 12 weeks against 16 weeks of treatment
Effect estimate
No reviewed effect estimate exists for this record.
Limits
This entry records a failure.
From the source
FUSION randomised 103 previously treated patients with genotype 2 or 3 to 12 weeks and 98 to 16 weeks of sofosbuvir plus ribavirin. Sustained virologic response was 50% at 12 weeks against 73% at 16 weeks, a difference of -23 percentage points (95% CI -35 to -11, p<0.001). In VALENCE the study was unblinded mid-course and genotype 3 treatment extended to 24 weeks on the strength of this signal, reaching 85% (95% CI 80 to 89) in 250 patients, but only 68% in those with cirrhosis against 91% without.
Written into the record, not signed off as a reviewed claim
No randomised trial has shown that curing hepatitis C prevents death or liver cancer
In plain words
Every trial on this page measures virus in blood. None of them counted deaths, cancers or transplants for long enough to say anything. The link between clearing the virus and living longer is inferred from observational follow-up, not from a randomised comparison.
What was measured
That sustained virologic response translates into fewer deaths, cirrhosis complications and liver cancers — biologically compelling, supported by cohort follow-up, and never tested against a randomised control
Effect estimate
No reviewed effect estimate exists for this record.
Limits
See the technical detail.
From the source
The Cochrane review by Jakobsen and colleagues pooled 138 randomised trials of 51 direct-acting antivirals in 25,232 participants, 128 of them placebo-controlled. It found no data at all on hepatitis C-related morbidity, and only limited mortality data from 11 trials (15 of 2,377 on DAA against 1 of 617 on control; OR 3.72, 95% CI 0.53 to 26.18, very low-quality evidence). None of the 138 trials provided usable data on ascites, variceal bleeding, hepato-renal syndrome, hepatic encephalopathy or hepatocellular carcinoma. Only one of 84 trials of marketed drugs measured quality of life. The authors concluded that SVR remains an outcome needing proper validation in randomised trials. The review was contested in print, and the counter-argument is that withholding a curative drug to run such a trial would now be unethical. Both things are true at once.
Written into the record, not signed off as a reviewed claim
The liver-cancer scare of 2016 did not survive adjustment for age and follow-up
In plain words
A Spanish study reported that liver cancers came back unusually often after these drugs cleared the virus, and it caused real alarm. A larger analysis found that the patients treated with the new drugs were older and followed for a shorter time, and once that was accounted for the difference disappeared.
What was measured
That direct-acting antivirals promote hepatocellular carcinoma — an inference from uncontrolled single-cohort rates that adjustment for age and follow-up time removes
Effect estimate
No reviewed effect estimate exists for this record.
Limits
See the technical detail.
From the source
Reig and colleagues reported radiologic tumour recurrence in 16 of 58 patients (27.6%) with previously treated hepatocellular carcinoma after interferon-free DAA therapy, at a median follow-up of 5.7 months, and called for large-scale assessment. Waziry and colleagues then meta-analysed 41 studies in 13,875 patients. Crude rates did look higher after DAA — HCC occurrence 2.96 per 100 person-years (95% CI 1.76 to 4.96) against 1.14 (0.86 to 1.52) after interferon; recurrence 12.16 (5.00 to 29.58) against 9.21 (7.18 to 11.81) — but DAA cohorts were older and followed for about a fifth as long. In meta-regression adjusting for follow-up and age, DAA therapy was associated with neither higher occurrence (RR 0.68, 95% CI 0.18 to 2.55, p=0.55) nor higher recurrence (RR 0.62, 95% CI 0.11 to 3.45, p=0.56).
Written into the record, not signed off as a reviewed claim
Two safety findings arrived after approval, one of them fatal
In plain words
Neither of these was seen in the trials. Combining sofosbuvir with the heart drug amiodarone can slow the heart dangerously, and one patient died. Separately, clearing hepatitis C can wake up a dormant hepatitis B infection, which has also caused deaths.
What was measured
Not recorded
Effect estimate
No reviewed effect estimate exists for this record.
Limits
This entry records a failure.
From the source
The label records postmarketing cases of symptomatic bradycardia and cases requiring pacemaker intervention when amiodarone was coadministered with a sofosbuvir-containing regimen, including one fatal cardiac arrest on ledipasvir/sofosbuvir. Onset was generally within hours to days and in some cases up to two weeks after starting treatment; bradycardia generally resolved on stopping. The label states the mechanism is unknown and does not recommend coadministration. Separately, the drug carries a boxed warning for hepatitis B virus reactivation in HCV/HBV coinfected patients, some cases resulting in fulminant hepatitis, hepatic failure and death, including in patients whose HBV appeared resolved (HBsAg negative, anti-HBc positive). Both findings came from postmarketing surveillance, not from the registration programme.
Source
SOVALDI United States prescribing information, boxed warning and Warnings and Precautions 5.1 and 5.2 (NDA 204671)
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 price was not derived from the cost of making the drug
In plain words
A twelve-week course launched at eighty-four thousand US dollars. A published model of what it costs to manufacture the same course at scale put the figure between sixty-eight and a hundred and thirty-six dollars. The same course was listed at twenty-five thousand in Spain.
What was measured
That the launch price reflected the cost of developing and making the drug — the published manufacturing projection and the fourfold spread across high-income countries are both inconsistent with it
Effect estimate
No reviewed effect estimate exists for this record.
Limits
See the technical detail.
From the source
Hill and colleagues classified four hepatitis C DAAs and ribavirin by chemical structure, molecular weight, daily dose and synthetic complexity, projected manufacturing cost per gram at a volume of one million courses per year, and benchmarked against actual generic antiretroviral costs of US$0.2 to US$2.1 per gram. Projected manufacturing cost for a 12-week course of sofosbuvir was US$68 to US$136, with ribavirin at US$21 to US$63; they ranked sofosbuvir third of five for synthetic complexity, below faldaprevir and simeprevir. Rosenthal and Graham record the United States wholesale acquisition cost at US$84,000 for the same course, against US$54,000 in the United Kingdom and US$25,000 in Spain, and note an average negotiated discount of 46% off WAC that is not public per contract.
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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
Everything above is built from what is below. This layer keeps the technical vocabulary, record identifiers and every stored row, so a reader who wants to check the page can.
The older medicine-wide conclusion held in this record
Written for a clinical reader, and about the medicine as a whole rather than about one indication, population and set of trials. RNAWiki does not treat it as a programme conclusion and no reviewer has signed it off in that form. It is here word for word because it is what the record holds.
A uridine nucleotide prodrug that the liver converts into a fake building block, which the hepatitis C polymerase inserts into its own genome and then cannot extend — 90% cure in 327 previously untreated patients in NEUTRINO and 78% against 0% on placebo in POSITRON, launched in the United States at US$84,000 for a twelve-week course against a published minimum manufacturing cost of US$68 to US$136.
Recorded evidence blocks (10)
Q2
On the Sofosbuvir label: indicated for what?
"SOVALDI is a hepatitis C virus (HCV) nucleotide analog NS5B polymerase inhibitor indicated for the treatment of: Adult patients with genotype 1, 2, 3 or 4 chronic HCV infection without cirrhosis or with compensated cirrhosis as a component of a combination antiviral treatment regimen. ( 1 ) Pediatric patients 3 years…": indications and usage on Sofosbuvir's label. DailyMed label · 80beab2c-396e-4a37-a4dc-40fdb62859cf · 2024-12-26
Q3
269 registered trials of Sofosbuvir — at which phases?
Registered studies posting no result
117 of 269
269 registered studies of Sofosbuvir: 100 phase2, 79 phase3, 45 phase4, 30 na or unstated, 17 phase1, 8 na, 3 early phase1. CLINICALTRIALS_SNAPSHOT · 2026-09-01
361 with a PubMed record
Show the evidence
phase2
100
phase3
79
phase4
45
na or unstated
30
phase1
17
na
8
11 more recorded rows
early phase1
3
completed
209
unknown
28
terminated
13
withdrawn
8
active not recruiting
4
no longer available
2
recruiting
2
approved for marketing
1
enrolling by invitation
1
not yet recruiting
1
recorded 2026-09-01 · last checked 2026-09-04
Q4
19 of Sofosbuvir's trials stopped: accrual/recruitment, funding/business, other?
27 hours; The median terminal half-lives of sofosbuvir and GS-331007 were 0.4 and 27 hours, respectively.
tmaxpharmacokinetics
0.5–2 hour; Following oral administration of SOVALDI, sofosbuvir was absorbed with a peak plasma concentration observed at ~0.5–2 hour post-dose, regardless of dose level.
metabolismpharmacokinetics
Metabolism Sofosbuvir is extensively metabolized in the liver to form the pharmacologically active nucleoside analog triphosphate GS-461203.
recorded 2024-12-26 · last checked 2026-09-04
Q7
Which running trial of Sofosbuvir could settle lifespan?
NCT03520660 measures Phase II: Liver-related clinical outcome, HCC, or liver-related mortality, reading out 2032-12-31.
1 open trial; n 121; "People With CHC Who Achieved a Sustained Virological Response Following Therapy With Direct Acting Antiviral Agents"
Show the evidence
TrialNCT03520660
"People With CHC Who Achieved a Sustained Virological Response Following Therapy With Direct Acting Antiviral Agents"; n 121; "Phase II: Liver-related clinical outcome, HCC, or liver-related mortality"; 2032-12-31
Q8
Which 66 trials of Sofosbuvir posted no result?
Posted no result
66 of 66 completed trials
Registrations
NCT01497327, NCT01435044, NCT02491450, NCT02278419, NCT02605798 and NCT02165189, and 60 more
Completion dates
oldest 2012-01; newest 2024-03-15
Show the evidence
Trial
NCT01497327
2012-01
NCT01435044
2013-05
NCT02491450
2015-02
NCT02278419
2015-10
NCT02605798
2015-10
NCT02165189
2015-11
14 further recorded trials
NCT02470858
2015-12
NCT02253550
2016-01
NCT02480387
2016-01
NCT02596880
2016-06
NCT02953535
2016-06
NCT02480686
2016-08
NCT03062423
2016-11
NCT03005210
2016-12
NCT03063723
2016-12-01
NCT03453346
2017-03-30
NCT02647632
2017-04
NCT03188276
2017-05-01
NCT02768961
2017-05-10
NCT04039958
2017-05-28
Q9
At the median, Sofosbuvir's trials enrolled 97.5 people — anything larger?
Median enrolment
97.5
Largest enrolment
50000
Registered trials counted
266
Q10
What do 17963 spontaneous reports say about Sofosbuvir — 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.
Sofosbuvir appears in spontaneous reports to regulators. Across the 10 most-reported reaction terms, 17963 reaction mentions were counted: fatigue 5835; headache 4869; hepatitis c 2390; insomnia 1287. FAERS via Open Targets · CHEMBL1259059 · 2026-06-24
Show the evidence
fatigue
5835
headache
4869
hepatitis c
2390
insomnia
1287
treatment failure
1057
hepatocellular carcinoma
1041
4 more recorded rows
ascites
435
hepatic failure
388
genotype drug resistance test positive
363
hepatic cirrhosis
298
recorded 2026-06-24 · last checked 2026-09-04
Q11
Which 10 reactions does Sofosbuvir's label not list?
ChEMBL 37 — CC BY-SA 3.0 Unported · 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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✓ source coverage passed: 6 source rows
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