This page shows what was measured, who it was measured in, and what that does not settle.
What Simeprevir does in the body
A discontinued United States treatment for two genetic forms of hepatitis C.
Hepatitis C builds all its proteins as one long strip and then cuts the strip into working parts with its own molecular scissors. Simeprevir jams the scissors, so the strip is never cut and the virus cannot assemble the machinery to copy itself. The problem is where it grips. Its contact point includes a spot on the enzyme that varies naturally between viruses, and in about three in ten of the commonest form of genotype 1 that spot is already different — enough that the drug binds roughly ten times less well before anyone has taken anything.
What happened in people
Adding it to older treatment raised cure from about 50 in 100 to 80 in 100.
✓ 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
A common natural virus change weakened it substantially and helped make the medicine obsolete.
Where it acts
Hepatocyte cytoplasm at the endoplasmic reticulum membrane, where the viral polyprotein is processed
Kind of result
The kind of result is not recorded
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 chemical.
FDA substance registry · 9WS5RD66HZ · read 2026-08-29
Its recorded molecular formula is C38H47N5O7S2, weighing 749.9.
PubChem record · 24873435 · read 2026-08-29
Where each sentence above came from
No recorded sentence describes the change this makes in a way that stands on its own. 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 126 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 the planned end of treatment, intention to treat
80% (210/264) against 50% (65/130); adjusted difference 29.3% (95% CI 20.1 to 38.6), p<0.0001
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. Treatment duration in the simeprevir arm was response-guided (24 or 48 weeks) while the placebo arm was fixed at 48 weeks, so duration was not held constant between the groups being compared.
How far it carries. This study is recorded from the curated record, not from the registry match.
Form and route. Oral capsule, once daily with food — no longer marketed in the United States
Interval reported. 95% CI 20
Written into the record, not signed off as a reviewed claim.
SVR12 in genotype 1 patients with cirrhosis, against a historical control rate of 70%
✓ The study showed what it set out to show
Who was studied
OPTIMIST-2 (NCT02114151)
How many people
103
Study design
Phase 3, open-label, single-arm, against a composite historical control
Compared against
Not recorded for this study
Kind of result
A number that stands in for health
What was found
83% (95% CI 76 to 91) against the 70% historical benchmark; 88% (44/50) treatment-naive and 79% (42/53) treatment-experienced
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 and open-label with a constructed comparator. Adverse events in 70% of patients and 3% discontinued all treatment for adverse events. Contemporaneous alternatives in the same population were reporting mid-nineties cure rates.
How far it carries. This study is recorded from the curated record, not from the registry match.
Form and route. Oral capsule, once daily with food — no longer marketed in the United States
Interval reported. 95% CI 76 to 91) against the 70% historical benchmark; 88% (44/50) treatment-naive and 79% (42/53) treatment-experienced
Written into the record, not signed off as a reviewed claim.
RNAWiki holds 3 written-up human studies for this substance, each with the question it asked.
How we know it
Each card names the study, the number of people and what the study set out to measure.
What this does not prove
These summaries were written by a person and have not been signed off as reviewed claims.
Why it matters
A study that failed is as informative as one that worked, and both are here.
What we still do not know
No reviewed claim exists, so no exact population, effect size or interval is published yet.
What it changes in the body◇Read from sources, not yet reviewed
The path through the body
From what a person takes to what changes. A solid line is a step measured in people. A dashed line is a step nobody has measured that way.
Start
Simeprevir
What a person takes: Oral capsule, once daily with food — no longer marketed in the United States.
The measurement behind this step
One 150 mg capsule once daily with food, in combination with sofosbuvir or with peginterferon alfa and ribavirin, for 12 weeks. Never available as a fixed-dose combination. The product has been discontinued in the United States.
Getting in
A test first, then one tablet a day
Genotype 1a patients were meant to be screened for the Q80K variant before starting, and if it was found the label pointed to a different drug.
──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
Simeprevir 150 mg once daily with food, in combination with sofosbuvir or with peginterferon alfa and ribavirin. The label strongly recommended NS3 Q80K screening in genotype 1a and consideration of alternative therapy if detected, and carried separate IFNL3 pharmacogenetic information about the patient.
The drug is taken up by liver cells and leaves in bile, and it is heavily bound to proteins in the blood.
──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
Taken up by OATP1B1 and metabolised by CYP3A, with biliary elimination. Very high plasma protein binding, and an extended aromatic system that absorbs in the near-ultraviolet — the chemical basis of the photosensitivity reported in trials.
It grips the viral scissors — at a spot that varies between viruses
Simeprevir sits in the enzyme’s cutting groove and blocks it. Its grip includes position 80, which naturally differs in about three in ten genotype 1a infections.
╌╌Measured in animals. A result in animals says what to test next. It does not say what happens in people.
The measurement behind this step
A fourteen-membered macrocyclic acylsulfonamide spanning the P1 to P3 subsites of the NS3/4A active site, which brings it into contact near residue 80. The Q80K substitution confers an approximately tenfold reduction in activity in vitro; the later P2-to-P4 macrocycles grazoprevir and glecaprevir move that contact away and are unaffected.
None of the individual viral proteins are released, so the copying machinery is never assembled.
╌╌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
NS3/4A cleaves the viral polyprotein at the NS3-NS4A, NS4A-NS4B, NS4B-NS5A and NS5A-NS5B junctions and also cleaves the host adaptor MAVS, so protease inhibition removes both the maturation step and the virus’s suppression of innate sensing.
Added to the interferon regimens of the time, it took sustained response from around 50% to around 80% — a real and properly controlled gain.
╌╌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
SVR12 80% (210/264) against 50% (65/130) in QUEST-1 and 81% (209/257) against 50% (67/134) in QUEST-2, both double-blind and placebo-controlled, with adjusted differences of 29.3 and 32.2 percentage points.
And then one letter of the virus decided the outcome
Q80K was present in nearly three in ten genotype 1a infections before treatment, lowered cure rates, and led to a label that recommended using something else. The drug is no longer licensed in the United States.
──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
Baseline Q80K in 29.5% of genotype 1a (269/911) and 0.5% of genotype 1b (5/1,096), conferring roughly tenfold potency loss. At failure, 91.4% of patients carried emerging mutations at positions 80, 122, 155 or 168 with more than fiftyfold resistance.
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.
Nobody in the United States. The NCBI Medical Genetics Summaries entry on simeprevir was archived in July 2020 with the note that simeprevir is no longer licensed for use in the USA. The record is kept here because the Q80K story is the reason later drugs were designed the way they were.
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
Q80K, a naturally occurring polymorphism present in nearly three in ten genotype 1a infections before any treatment
A label that strongly recommended screening for it and strongly recommended considering alternative therapy if found
A second pharmacogenetic marker, IFNL3, with lower response in CT and TT genotypes
Photosensitivity and rash attributable to the molecule’s own aromatic system
The highest projected manufacturing cost of the five hepatitis C antivirals independently costed
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
Withdrawn
❝ 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 capsule, once daily with food — no longer marketed in the United States
✎ 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.
A register records the withdrawal of an approval.
No source is stored against this line.
What is in the pack
One 150 mg capsule once daily with food, in combination with sofosbuvir or with peginterferon alfa and ribavirin, for 12 weeks. Never available as a fixed-dose combination. The product has been discontinued in the United States.
✎ 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
Rash occurred in 24% against 11% on placebo and photosensitivity in 4% against under 1% in QUEST-2; the photosensitivity follows from the molecule’s extended aromatic system rather than from the regimen. Transient hyperbilirubinaemia without transaminase change is characteristic and reflects inhibition of bilirubin transporters rather than liver injury. Simeprevir is an OATP1B1 substrate and a CYP3A substrate, so strong inducers reduce exposure substantially. Discontinuation for adverse events was under 1% in QUEST-1 and 3% in the cirrhotic OPTIMIST-2 population.
Nobody counted how many people took this and were fine, so this cannot be turned into a rate.
Over a long time. No completed tested study window is recorded, so long-term effects are not established by the registry record.
Groups the studies covered thinly. Which groups were under-represented in the studies has not been recorded for this substance. Pregnancy, breastfeeding, children, older adults, and people with liver or kidney conditions are commonly excluded from trials; nothing here says whether they were.
What is missing or unclear∅Nothing found in the sources checked
Does the exact form matter?
Evidence belongs to the exact thing that was tested. A different salt, a different mixture or a different preparation is a different question.
The form that was studied
Oral capsule, once daily with food — no longer marketed in the United States
✎ 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
Never available as a fixed-dose combination. The product has been discontinued in the United States.
✎ Source-linked record
Where this came from
A person wrote this into the record with the study named beside it. No reviewer has signed it off.
Recorded notes on which forms are sold and how they compare.
No source is stored against this line.
Evidence carries across two names for one substance. It does not carry across a salt, a mirror form or a mixture.
What it would be like to take◇Read from sources, not yet reviewed
What you could measure
This one is decided with a clinician, so this section holds questions to ask rather than a plan to run.
Self-experiment planning is not offered for a prescription or clinician-supervised medicine, withdrawn medicine. The questions below are for a clinician or pharmacist.
Questions worth asking
Which of the trials of Simeprevir 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 83% in cirrhosis was a competitive result — it was superiority against a 70% historical benchmark, not against a concurrent comparator
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 resistance had resolved in the half of failures where it became undetectable; population sequencing sees only variants above roughly 15 to 20% of the population
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 QUEST comparisons isolate simeprevir cleanly; the simeprevir arm used response-guided durations of 24 or 48 weeks against a fixed 48 weeks on placebo
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 tenfold in-vitro potency loss predicts the size of the clinical loss; the authors report Q80K had only a minor effect on initial response and a larger one on sustained response
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 Simeprevir 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.
QUEST-1 and QUEST-2: 80% and 81% against 50% on placebo
In plain words
Two double-blind trials gave everyone the same interferon and ribavirin and randomised only whether they also took simeprevir. Half the placebo patients were cured; four in five of the simeprevir patients were.
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
QUEST-1 randomised 394 treatment-naive genotype 1 patients 2:1 to simeprevir 150 mg daily or placebo, each with peginterferon alfa-2a and ribavirin, double-blind, in 13 countries. SVR12 was 80% (210/264) against 50% (65/130), adjusted difference 29.3% (95% CI 20.1 to 38.6), p<0.0001. QUEST-2 randomised 391 patients on the same design with peginterferon alfa-2a or alfa-2b: SVR12 81% (209/257) against 50% (67/134), adjusted difference 32.2% (95% CI 23.3 to 41.2), p<0.0001. Adverse events led to discontinuation of simeprevir in under 1% in QUEST-1. These are properly controlled results and they are the reason the drug was approved.
Written into the record, not signed off as a reviewed claim
Q80K: present in 29.5% of genotype 1a before treatment, worth about tenfold
In plain words
One naturally occurring change at position 80 of the viral enzyme makes simeprevir roughly ten times weaker. It is not caused by treatment — nearly three in ten people with the commonest form of genotype 1 already have it.
What was measured
Baseline Q80K prevalence 29.5% in genotype 1a (269/911), conferring an approximately tenfold in-vitro potency loss
Effect estimate
No reviewed effect estimate exists for this record.
Limits
This entry records a failure.
From the source
Baseline sequencing was available for 2,007 genotype 1 simeprevir-treated patients across the phase 2b and 3 programme. Baseline NS3 polymorphisms at positions associated with reduced in vitro susceptibility — 43, 80, 122, 155, 156 or 168, defined as an EC50 fold-change above 2.0 — were uncommon at 1.3% (26/2,007), with one exception. Q80K, which confers approximately a tenfold reduction in simeprevir activity in vitro, was present in 13.7% overall (274/2,007): 29.5% of genotype 1a (269/911) and 0.5% of genotype 1b (5/1,096). The authors report that baseline Q80K had only a minor effect on initial response but resulted in lower sustained virologic response rates. The distinction matters: a variant that does not change the early viral decline but changes the cure rate is invisible in the on-treatment data and only appears at the endpoint.
Written into the record, not signed off as a reviewed claim
A label that told prescribers to consider a different drug
In plain words
The approved label strongly recommended testing genotype 1a patients for Q80K before treatment, and strongly recommended considering alternative therapy if it was found. Very few labels tell a doctor to use something else.
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 NCBI Medical Genetics Summaries entry on simeprevir records that the FDA-approved label strongly recommends that patients with HCV genotype 1a infection be screened for the presence of virus with the NS3 Q80K polymorphism, and that if Q80K is detected, the label strongly recommends that alternative therapy be considered. The same entry notes the label’s IFNL3 (formerly IL28B) pharmacogenetic information, with lower response rates in CT and TT genotypes than in CC. Two separate pre-treatment genetic tests — one on the virus, one on the patient — for a single twelve-week drug is a strong signal about how narrow the population of reliable responders was.
Source
Dean L. Simeprevir therapy and IFNL3 genotype. In: Medical Genetics Summaries. Bethesda (MD): NCBI; 2016, updated 2020 (PMID 28520373)
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
Nine in ten failures ended with high-level resistance, and half of it then vanished from view
In plain words
Almost every patient in whom the drug failed ended up carrying virus that was more than fifty times less susceptible to it. Half of those mutations were no longer detectable six months later — not necessarily gone, just below what the test can see.
What was measured
91.4% (180/197) of failures with emerging high-level resistance; undetectable by population sequencing in 50% at median 28.4 weeks
Effect estimate
No reviewed effect estimate exists for this record.
Limits
This entry records a failure.
From the source
Among simeprevir-treated patients without sustained virologic response, 91.4% (180/197) had emerging mutations at NS3 positions 80, 122, 155 and/or 168 at failure, mainly R155K in genotype 1a with and without Q80K and D168V in genotype 1b, conferring EC50 fold-changes above 50. Emerging mutations were no longer detectable by population sequencing at study end in 50% (90/180), at a median follow-up of 28.4 weeks. Population sequencing detects variants above roughly 15 to 20% of the viral population; disappearance from that assay means the variant fell below the threshold, not that it was cleared, and archived resistance can persist in the replication-competent pool. Reporting only the later timepoint would understate what a simeprevir failure leaves behind for the next regimen.
Written into the record, not signed off as a reviewed claim
OPTIMIST-2 declared superiority against a historical control of 70%
In plain words
The trial in cirrhotic patients cured 83% and was reported as beating its comparator. The comparator was a 70% figure assembled from earlier studies, not a group of patients treated at the same time.
What was measured
That an 83% cure rate in cirrhosis represented a competitive result — it was superior to a 70% historical benchmark and below what concurrent alternatives were reporting
Effect estimate
No reviewed effect estimate exists for this record.
Limits
See the technical detail.
From the source
OPTIMIST-2 was a phase 3, open-label, single-arm study of 12 weeks of simeprevir with sofosbuvir in 103 genotype 1 patients with documented cirrhosis. The primary endpoint was SVR12 against a composite historical control of 70%. SVR12 was 83% (95% CI 76 to 91), meeting superiority against that benchmark; treatment-naive patients reached 88% (44/50) and treatment-experienced 79% (42/53). Adverse events occurred in 70%, mostly grade 1 or 2, and 3% discontinued all study treatment for adverse events. The design is the audit: 83% was a statistically superior result against a constructed benchmark at a moment when contemporaneous regimens in cirrhotic genotype 1 patients were reporting figures in the mid-nineties. Superiority against a historical control is a claim about a number, not about a comparison a patient would recognise.
Written into the record, not signed off as a reviewed claim
Rash in a quarter of patients and photosensitivity in one in twenty-five
In plain words
A quarter of people on simeprevir developed a rash, against one in nine on placebo, and photosensitivity reactions were several times more common.
What was measured
Rash 24% against 11% and photosensitivity 4% against under 1% in QUEST-2
Effect estimate
No reviewed effect estimate exists for this record.
Limits
This entry records a failure.
From the source
In QUEST-2, rash occurred in 24% (61/257) of simeprevir patients against 11% (15/134) on placebo, and photosensitivity in 4% (10/257) against under 1% (1/134). In QUEST-1, using peginterferon alfa-2a alone as the backbone, rash frequencies were similar between groups at 27% and 25%, and anaemia at 16% and 11%. The photosensitivity is chemically unsurprising: simeprevir carries an extended methoxy-quinoline and thiazole aromatic system that absorbs in the near-ultraviolet, and the effect is a property of the molecule rather than of the combination.
Written into the record, not signed off as a reviewed claim
From approved in 2013 to unlicensed in the United States by 2020
In plain words
Simeprevir was approved in late 2013, and within a few years it had been removed from the American market. Nothing was discovered that made it dangerous; better drugs simply made its limitations unacceptable.
What was measured
Not recorded
Effect estimate
No reviewed effect estimate exists for this record.
Limits
See the technical detail.
From the source
The NCBI Medical Genetics Summaries entry on simeprevir was archived on 15 July 2020 with the explicit note that simeprevir is no longer licensed for use in the USA. The reasons are all visible in the data above: a pre-treatment viral genetic test whose positive result pointed to a different drug, a second pharmacogenetic marker in the patient, a 29.5% baseline prevalence of the defeating polymorphism in the commonest subtype it treated, 83% in cirrhosis when competitors were reporting mid-nineties, and photosensitivity. This is what a drug being outcompeted looks like from the inside, and it is worth recording because the specific failure — a common natural polymorphism at the binding interface — became a design constraint every subsequent protease inhibitor was built against.
Source
Dean L. Simeprevir therapy and IFNL3 genotype. In: Medical Genetics Summaries. Bethesda (MD): NCBI; 2016, updated and archived 15 July 2020 (PMID 28520373)
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
The most complex hepatitis C molecule to make of the five that were costed
In plain words
An independent analysis ranked simeprevir the hardest to synthesise of the five hepatitis C drugs it examined, and projected a manufacturing cost of US$130 to US$270 per twelve-week course.
What was measured
Projected minimum manufacturing cost US$130 to US$270 per 12-week course, the highest of the five drugs assessed
Effect estimate
No reviewed effect estimate exists for this record.
Limits
See the technical detail.
From the source
The retrosynthesis-based cost analysis ranked complexity of chemical synthesis from lowest to highest as ribavirin, daclatasvir, sofosbuvir, faldaprevir and simeprevir, and projected minimum manufacturing costs per 12-week course of US$21 to US$63 for ribavirin, US$10 to US$30 for daclatasvir, US$68 to US$136 for sofosbuvir, US$100 to US$210 for faldaprevir and US$130 to US$270 for simeprevir. The complexity is visible in the structure: a fourteen-membered macrocycle formed by ruthenium-catalysed metathesis, three contiguous stereocentres on a cyclopentane, an aryl ether coupling to a substituted quinoline, and an acylsulfonamide warhead. No pricing block appears on this page because the drug is no longer marketed in the United States and no current acquisition price could be verified against a checkable dataset.
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
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 once-daily NS3/4A protease inhibitor that raised sustained virologic response from 50% to 80% and 81% against placebo in two double-blind trials totalling 785 patients, and that was then undone by Q80K — a naturally occurring change present in 29.5% of genotype 1a infections before treatment, costing about tenfold of potency, prompting a label that told doctors to consider alternative therapy if the test was positive, and ending with the drug no longer licensed in the United States.
Recorded evidence blocks (7)
Q1
45 registered trials of Simeprevir — at which phases?
accrual/recruitment (1), funding/business (1), sponsor decision unspecified (1) and other (3): Simeprevir's stop wording, clustered. CLINICALTRIALS_SNAPSHOT · 2026-09-01
"Study terminated due to the Sponsor's decision."; 6 of 45 registered studies
Show the evidence
Trial
NCT02118597
terminated; "Study terminated due to the Sponsor's decision."
NCT02206932
withdrawn; "never opened"
NCT02397395
withdrawn; "Trial has been cancelled due to availability of new therapeutic options for patient population"
NCT02455167
terminated; "Study stopped due to low accrual and availability of other treatment options"
NCT02485080
withdrawn; "Withdrawn due to lack of resources"
NCT03059303
terminated; "Decision to discontinue development of investigational Hep C treatment regimen JNJ-4178: 3 direct acting antivirals - AL-335, ODV \& SMV."
recorded 2026-09-01 · last checked 2026-09-04
Q3
Human studies of Simeprevir used TMC435350 200 mg — over how long?
Human studies of Simeprevir used "TMC435350 200 mg". ClinicalTrials.gov · 2026-09-01
4 recorded entries; human; also "Simeprevir 150 mg", "Simeprevir (SMV) 150 mg", "Simeprevir 75 mg"
Show the evidence
human
NCT01891851
TMC435350 200 mg
NCT02349048
Simeprevir 150 mg
NCT02397395
Simeprevir (SMV) 150 mg
NCT03059303
Simeprevir 75 mg
recorded 2026-09-01 · last checked 2026-09-04
Q4
Which 21 trials of Simeprevir posted no result?
Posted no result
21 of 21 completed trials
Registrations
NCT01891851, NCT00752544, NCT00741169, NCT00752648, NCT01707342 and NCT01813513, and 15 more
Completion dates
oldest 2008-01; newest 2019-12
Show the evidence
Trial
NCT01891851
2008-01
NCT00752544
2008-11
NCT00741169
2008-12
NCT00752648
2009-01
NCT01707342
2012-11
NCT01813513
2013-07
14 further recorded trials
NCT01907724
2013-08
NCT01852604
2015-04
NCT02512562
2015-08-31
NCT02385071
2015-09-09
NCT02278419
2015-10
NCT02165189
2015-11
NCT02470858
2015-12
NCT02253550
2016-01
NCT02824315
2016-10
NCT02885454
2016-12
NCT02945020
2017-01-20
NCT02333292
2017-06-30
NCT02771405
2018-01
NCT03549832
2019-01-30
Q5
At the median, Simeprevir's trials enrolled 40 people — anything larger?
Median enrolment
40
Largest enrolment
10000
Registered trials counted
45
Q6
What do 511 spontaneous reports say about Simeprevir — 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.
Simeprevir appears in spontaneous reports to regulators. Across the 10 most-reported reaction terms, 511 reaction mentions were counted: hepatitis c 130; anaemia 80; photosensitivity reaction 68; blood bilirubin increased 62. FAERS via Open Targets · CHEMBL3137358 · 2026-06-24
Show the evidence
hepatitis c
130
anaemia
80
photosensitivity reaction
68
blood bilirubin increased
62
hepatocellular carcinoma
41
hyperbilirubinaemia
37
4 more recorded rows
sunburn
25
blister
24
ascites
22
jaundice
22
recorded 2026-06-24 · last checked 2026-09-04
Q9
Where do the label and the trials disagree about Simeprevir?
"withdrawn" against "approved": withdrawal status vs register status for Simeprevir.
EMA_MEDICINE_REGISTER, Drugs@FDA; 1 recorded pair
Show the evidence
EMA_MEDICINE_REGISTEREMEA/H/C/002777
withdrawn; 2026-09-04
Drugs@FDANDA205123
approved; 2026-08-28
Where it is registered
Where it’s registered
Withdrawn, in European Union; no reason is published (EMA Medicine.csv)
ChEMBL 37 — CC BY-SA 3.0 Unported · ClinicalTrials.gov — US Government work · EMA medicine register · Open Targets 26.06 — CC0 · mixed register set; per-register licences in docs/specs/corpus-20k-sources.md
✗ required summary fields resolved: 4 required field(s) not terminal: Why people use it, Best-supported result, Biggest unanswered question, Human evidence
✓ public claims reviewed: 0 reviewed claim(s); drafts are never rendered
✓ source coverage passed: 6 source rows
✓ no critical contamination: no quarantine open
✓ canonical metadata passed: slug and display name present
✓ no raw internal fields: enforced by the copy-contract test over the rendered page
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