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Telbivudine

  • Withdrawn substance
  • Withdrawn
  • Identity checked
  • Sources last checked 2026-09-04

This page shows what was measured, who it was measured in, and what that does not settle.

What Telbivudine does in the body

Telbivudine is a mirror-image version of thymidine, one of the four building blocks of DNA.

Cells add three phosphates to it, and the hepatitis B copying enzyme picks it up instead of the real thing. Once it is in the chain, the chain cannot be extended, so copying stops. Being a mirror image is what makes it selective for the viral enzyme rather than the human one — and it is also, in ways that were never fully explained, connected to the muscle and nerve problems that ended the drug.

Why people take it. Long-standing hepatitis B infection — a drug that is no longer marketed in the United States

What happened in people

Therapeutic response 75.3% against 67.0% at week 52 and 63% against 48% at week 104 in HBeAg-positive patients, double-blind against lamivudine

Source-linked record

Where this came from

A person wrote this into the record with the study named beside it. No reviewer has signed it off.

The recorded finding that sits closest to something a person would notice. Written into the record, not signed off, and it carries no population or interval.

The limit that matters most

That superiority to lamivudine implied a competitive place in therapy — entecavir was already approved and was never the comparator

Where it acts
Hepatocyte cytoplasm for the antiviral effect — and skeletal muscle and peripheral nerve, which is where its characteristic toxicity appears
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 · 2OC4HKD3SF · read 2026-08-29

  • Its recorded molecular formula is C10H14N2O5, weighing 242.23.

    PubChem record · 159269 · read 2026-08-29

Where each sentence above came from

A person wrote this explanation into the record, with the studies named in the path below.

The recorded use, written for a reader without medical training. Not signed off.

A limit recorded against this substance. Not signed off as a reviewed claim.

The four opening statements run to 127 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.

Placebo

A placebo is a dummy treatment given so the real one can be compared with it.

A picture of it, and where the picture fails

A placebo is like a blank control in an experiment.

Where that stops being true. A blank does nothing. People given a placebo often do get better.

What people get wrong. A placebo effect is read as imaginary. The improvement is measured and real.

An inactive intervention matched in appearance to the test intervention, used to control for non-specific effects.

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.

What happened in peopleRead 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.

Therapeutic response — HBV DNA below 5 log10 copies/mL with either HBeAg loss or ALT normalisation — tested for non-inferiority to lamivudine

The study showed what it set out to show

Who was studied
GLOBE (Lai 2007, N Engl J Med; Liaw 2009, Gastroenterology)
How many people
1370
Study design
Phase 3, randomised, double-blind, active-controlled against lamivudine
Compared against
Not recorded for this study
Kind of result
A number that stands in for health
What was found
Week 52: 75.3% against 67.0% (P=0.005) in HBeAg-positive patients. Week 104: 63% against 48% (P<0.001) and 78% against 66% (P=0.007); resistance 25.1% against 39.5% and 10.8% against 25.9%
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 composite endpoint threshold of 5 log10 copies/mL is more than a hundredfold above the assay’s 300 copies/mL limit of detection. Grade 3 or 4 creatine kinase elevations occurred in 12.9% against 4.1%. The comparator was the weakest licensed agent, and entecavir had been approved a year before this trial reported.

How far it carries. This study is recorded from the curated record, not from the registry match.

Form and route. Oral tablet and oral solution — both discontinued in the United States

Interval reported. Not recorded in this summary

Written into the record, not signed off as a reviewed claim.

Antiviral efficacy and safety of telbivudine with peginterferon alfa-2a against either alone

The study did not show it

Who was studied
Telbivudine plus peginterferon alfa-2a (Marcellin 2015, J Hepatol)
How many people
159
Study design
Randomised, open-label, three-arm — terminated early
Compared against
Not recorded for this study
Kind of result
A number that stands in for health
What was found
Undetectable HBV DNA at week 24 in 71% (12/17) on combination against 35% (17/48) on telbivudine (P=0.022) and 7% (3/42) on peginterferon (P<0.0001)
Repeated elsewhere
Failed to Replicate

What this does not prove. A study that did not show an effect does not show that no effect exists anywhere.

The limits of this study, and where it came from

Main limit. Terminated at 159 of 300 planned patients because of peripheral neuropathy in 7 of 50 on combination therapy against 1 of 54 and 0 of 54. The most virologically effective arm was the reason the trial was stopped, and the authors conclude the combination should not be used.

How far it carries. This study is recorded from the curated record, not from the registry match.

Form and route. Oral tablet and oral solution — both discontinued in the United States

Interval reported. Not recorded in this summary

Written into the record, not signed off as a reviewed claim.

What we know
RNAWiki holds 2 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 bodyRead 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.

  1. Start

    Telbivudine

    What a person takes: Oral tablet and oral solution — both discontinued in the United States.

    The measurement behind this step

    One 600 mg tablet once daily, or the 100 mg/5 mL oral solution, taken indefinitely, with the dosing interval lengthened as renal function falls. Both presentations are recorded as discontinued in Drugs@FDA under NDA 022011 and NDA 022154.

  2. Getting in

    One 600 mg tablet a day

    A single daily tablet, taken indefinitely, with creatine kinase checked because of the muscle problem.

    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

    Telbivudine 600 mg once daily with or without food. Renally cleared, so the dosing interval must be lengthened as creatinine clearance falls. Both United States presentations — the 600 mg tablet under NDA 022011 and the 100 mg/5 mL oral solution under NDA 022154 — are recorded as discontinued.

  3. Reaching the cell

    A mirror image of a natural building block

    Telbivudine is thymidine built the wrong way round. That reversed geometry is what lets the viral enzyme accept it while human enzymes largely do not.

    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 beta-L enantiomer of thymidine, phosphorylated by cellular kinases to the triphosphate. The unnatural L configuration is the basis of its selectivity for HBV reverse transcriptase over human DNA polymerases — and it is why an enantiomeric impurity in manufacture would simply be thymidine.

  4. What it acts on

    It is inserted, and the chain stops

    The viral copying enzyme picks it up instead of the real building block, and then finds it has nothing to attach the next piece to.

    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

    Telbivudine triphosphate competes with thymidine triphosphate at the HBV reverse transcriptase and terminates the growing DNA chain. It has no meaningful activity against HIV or other viruses.

  5. The change it makes

    Virus falls further than on lamivudine

    More patients reached undetectable virus than on the older drug — 56% against 39% in one group and 82% against 57% in the other.

    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

    Undetectable viraemia below 300 copies/mL at week 104 in 55.6% of HBeAg-positive telbivudine patients against 38.5% on lamivudine, and 82.0% against 56.7% in HBeAg-negative patients. Therapeutic response 63% against 48% and 78% against 66%.

  6. What that does for a person

    But escape needs only one mutation

    The virus needs a single change at one position to get past it — the same position that defeats lamivudine. A quarter of patients had made that change within two years.

    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

    Resistance maps to rtM204I, a single substitution, giving 25.1% resistance at week 104 in HBeAg-positive patients. Entecavir requires the rtM204 substitutions plus a second-site change at rtT184, rtS202 or rtM250, and reaches 1.2% at week 240.

  7. What that does for a person

    And the muscles and nerves paid for it

    Severe muscle enzyme rises in one patient in eight, and a combination trial with interferon stopped early after seven of fifty patients developed nerve damage.

    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

    Grade 3 or 4 creatine kinase elevation in 12.9% against 4.1% on lamivudine over two years. Peripheral neuropathy in 7 of 50 on telbivudine with peginterferon alfa-2a against 1 of 54 and 0 of 54 in the monotherapy arms, terminating that trial at 159 of 300 planned patients.

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 unclearRead 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. Both Tyzeka presentations are recorded as discontinued in Drugs@FDA. The record is kept because the reasons it lost are measurable and instructive.

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

  • A single-mutation escape route at rtM204I, the same position that defeats lamivudine, giving 25.1% resistance by two years
  • Grade 3 or 4 creatine kinase elevations in 12.9% of patients, three times the comparator rate
  • The peginterferon combination trial terminated early for peripheral neuropathy, despite being the most effective arm
  • A composite primary endpoint whose viral threshold sat more than a hundredfold above the limit of detection
  • Both United States presentations recorded as discontinued in Drugs@FDA
  • 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 takeRead 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 takeRead 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 tablet and oral solution — both 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.

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 600 mg tablet once daily, or the 100 mg/5 mL oral solution, taken indefinitely, with the dosing interval lengthened as renal function falls. Both presentations are recorded as discontinued in Drugs@FDA under NDA 022011 and NDA 022154.

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 takeRead 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

Myopathy is the characteristic toxicity: grade 3 or 4 creatine kinase elevations occurred in 12.9% of patients over two years against 4.1% on lamivudine, and unexplained muscle aches, tenderness or weakness are the symptoms to report. Peripheral neuropathy is the nerve counterpart, and the trial combining telbivudine with peginterferon alfa-2a was terminated early after it occurred in 7 of 50 combination-arm patients; that combination should not be used. As with every hepatitis B nucleos(t)ide, severe acute exacerbations of hepatitis have been reported after discontinuation, because the nuclear cccDNA reservoir is never cleared, and lactic acidosis with severe hepatomegaly and steatosis is a class effect. Overall adverse event frequency in GLOBE was similar to lamivudine.

Nobody counted how many people took this and were fine, so this cannot be turned into a rate.

Where this came from

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 unclearNothing 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 tablet and oral solution — both 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.

The form used in the studies cited on this page.

No source is stored against this line.

What is sold

Both presentations are recorded as discontinued in Drugs@FDA under NDA 022011 and NDA 022154.

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 takeRead 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 Telbivudine 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 unclearRead 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 superiority to lamivudine implied a competitive place in therapy — entecavir was already approved and was never the 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 a 63% "therapeutic response" describes viral control; the threshold was 100,000 copies/mL and undetectable viraemia was reported separately

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 telbivudine reduces cancer or decompensation — inferred through lamivudine’s outcome trial and telbivudine’s surrogate superiority, never tested directly

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 two-year resistance figure describes the long run; the curve was still rising and treatment is indefinite

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 unclearRead 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 Telbivudine 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 peopleRead 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.

GLOBE: it genuinely did beat lamivudine, in 1,370 double-blind patients
In plain words
A large double-blind trial compared telbivudine against lamivudine for a year. Telbivudine did better on the trial’s composite endpoint and on liver biopsy, and reduced the virus further.
What was measured
Therapeutic response 75.3% against 67.0% and histologic response 64.7% against 56.3% at week 52
Effect estimate
No reviewed effect estimate exists for this record.
Limits
See the technical detail.
From the source
GLOBE randomised 1,370 patients with chronic hepatitis B to telbivudine 600 mg or lamivudine 100 mg once daily, double-blind. The primary endpoint was non-inferiority for therapeutic response, defined as HBV DNA below 5 log10 copies/mL together with either HBeAg loss or ALT normalisation. At week 52, HBeAg-positive patients had a therapeutic response in 75.3% against 67.0% (P=0.005) and a histologic response in 64.7% against 56.3% (P=0.01); telbivudine was non-inferior in HBeAg-negative patients. Telbivudine was superior in both populations on mean HBV DNA reduction, on the proportion reaching undetectable by PCR, and on resistance. Elevated creatine kinase was more common on telbivudine and elevated ALT and AST more common on lamivudine.
Source
Lai CL et al., N Engl J Med 2007;357:2576-2588 (GLOBE Study Group)
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 comparator was the weakest drug in the class, a year after a far better one arrived
In plain words
Telbivudine was measured against lamivudine, which by then was known to fail in about half of patients within five years. Entecavir had been approved a year earlier and was far better than either. The two were never compared.
What was measured
That superiority to lamivudine implied a competitive place in therapy — the relevant comparator was already approved and was never tested against it
Effect estimate
No reviewed effect estimate exists for this record.
Limits
See the technical detail.
From the source
GLOBE ran against lamivudine 100 mg. In the randomised cirrhosis trial that established the value of treating hepatitis B at all, genotypic YMDD resistance emerged in 49% of lamivudine-treated patients over a median 32 months, so lamivudine’s resistance liability was published and known before GLOBE reported. Entecavir was approved in March 2005, more than a year before telbivudine’s October 2006 approval, with cumulative resistance of 0.5% at 96 weeks and 1.2% at 240 weeks in nucleoside-naive patients. No registrational trial compared telbivudine with entecavir. A superiority claim against the weakest available agent is a true statement about a comparison nobody needed made, and it is the single fact that best explains this drug’s commercial trajectory.
Source
Lai CL et al., N Engl J Med 2007;357:2576-2588; Liaw YF et al., N Engl J Med 2004;351:1521-1531; BARACLUDE United States prescribing information, resistance in clinical studies
Role in the trial
Not matched to a registered study
Identity check
no open identity hold
Audit mark
contested
Review state
Written into the record, not signed off as a reviewed claim
A quarter of patients had resistant virus by two years
In plain words
By the end of the second year, 25% of HBeAg-positive patients on telbivudine carried resistant virus. That was better than lamivudine’s 40%, and roughly twenty-five times the rate of the drug already on the market.
What was measured
Viral resistance 25.1% (HBeAg-positive) and 10.8% (HBeAg-negative) at week 104
Effect estimate
No reviewed effect estimate exists for this record.
Limits
This entry records a failure.
From the source
At week 104 of GLOBE, viral resistance had emerged in 25.1% of HBeAg-positive telbivudine patients against 39.5% on lamivudine (P<0.001), and in 10.8% against 25.9% of HBeAg-negative patients (P<0.001). Therapeutic response was 63% against 48% (P<0.001) and 78% against 66% (P=0.007), with undetectable viraemia below 300 copies/mL in 55.6% against 38.5% and 82.0% against 56.7%. The reason for the resistance rate is structural: telbivudine escape requires a single substitution at rtM204, the same position lamivudine resistance maps to, whereas entecavir requires those substitutions plus a further change at rtT184, rtS202 or rtM250. Escape that needs one mutation rather than three is a categorical difference, and it shows up as 25.1% at two years against 1.2% at five.
Source
Liaw YF et al., Gastroenterology 2009;136:486-495 (2-year GLOBE results); entecavir comparison from BARACLUDE United States prescribing information
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 combination trial was stopped early for peripheral neuropathy in 7 of 50
In plain words
A trial combining telbivudine with peginterferon was suppressing the virus better than either drug alone, and was terminated anyway because seven of the fifty patients on the combination developed nerve damage.
What was measured
Peripheral neuropathy in 7 of 50 on combination therapy against 1 of 54 and 0 of 54; trial terminated at 159 of 300 planned patients
Effect estimate
No reviewed effect estimate exists for this record.
Limits
This entry records a failure.
From the source
A randomised, open-label, multicentre study in treatment-naive HBeAg-positive patients compared telbivudine with peginterferon alfa-2a, telbivudine alone and peginterferon alone. It was terminated early after 159 of a planned 300 patients were randomised, because of increased rates of peripheral neuropathy in the combination group. Peripheral neuropathy occurred in 7 of 50 on combination therapy, 1 of 54 on telbivudine and 0 of 54 on peginterferon. At week 24, undetectable HBV DNA below 300 copies/mL was reached by 71% (12/17) on combination therapy, 35% (17/48) on telbivudine and 7% (3/42) on peginterferon (P=0.022 and P<0.0001). The authors state that despite the rapid and profound reductions in HBV DNA, combination therapy with telbivudine and peginterferon should not be used. This is the rare case where the most effective arm in a trial is the one that gets it stopped.
Source
Marcellin P et al., J Hepatol 2015;62:41-47
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
Grade 3 or 4 creatine kinase elevations in one patient in eight
In plain words
Muscle enzyme levels rose to severe grades in nearly 13% of patients on telbivudine, against 4% on the comparator. Muscle and nerve toxicity is the characteristic problem of this molecule.
What was measured
Grade 3 or 4 creatine kinase elevation 12.9% against 4.1% over two years
Effect estimate
No reviewed effect estimate exists for this record.
Limits
This entry records a failure.
From the source
Over the two-year GLOBE period, grade 3 or 4 increases in creatine kinase occurred in 12.9% of telbivudine patients against 4.1% on lamivudine (P<0.001), while overall adverse event frequency was similar. Creatine kinase is released from damaged skeletal muscle, and myopathy is the recognised class problem for this molecule; the separate peripheral neuropathy signal in the peginterferon combination trial is the nerve counterpart. A 12.9% rate of severe biochemical muscle injury in a drug taken indefinitely, when a better-tolerated and more effective alternative was already licensed, is the practical explanation for why this drug did not survive.
Source
Liaw YF et al., Gastroenterology 2009;136:486-495 (2-year GLOBE results)
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 primary endpoint was a composite, and its viral threshold was not undetectable
In plain words
The trial’s main endpoint counted a patient as a success at a viral load more than a hundred times above the limit of detection, provided one of two other things had also happened.
What was measured
That a 75.3% or 63% "therapeutic response" means the virus was controlled — the threshold was 100,000 copies/mL, and undetectable viraemia was reported separately and lower
Effect estimate
No reviewed effect estimate exists for this record.
Limits
See the technical detail.
From the source
Therapeutic response was defined as HBV DNA below 5 log10 copies/mL — that is, below 100,000 copies/mL — together with either HBeAg loss or ALT normalisation. The assay’s limit of detection in the same trial was 300 copies/mL, and the trial reports undetectable viraemia separately at 55.6% and 82.0%. So the headline 75.3% and 63% figures include patients still carrying tens of thousands of viral copies per millilitre. The composite also joins an immunological event (HBeAg loss) and a biochemical one (ALT normalisation) with an "or", meaning two patients counted as responders may share nothing except the viral threshold. None of this is hidden — the paper reports the components — but the number most often quoted is the composite.
Source
Lai CL et al., N Engl J Med 2007;357:2576-2588; Liaw YF et al., Gastroenterology 2009;136:486-495
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
Both United States presentations are recorded as discontinued
In plain words
Tyzeka is gone from the American market. The tablet and the oral solution are both listed as discontinued in the FDA’s own database.
What was measured
Not recorded
Effect estimate
No reviewed effect estimate exists for this record.
Limits
See the technical detail.
From the source
Drugs@FDA records NDA 022011 (TYZEKA, telbivudine 600 mg tablet, Novartis) and NDA 022154 (TYZEKA, telbivudine 100 mg/5 mL oral solution, Novartis) with a marketing status of Discontinued. Nothing about the drug changed to cause this; what changed was the comparison. It was approved in October 2006 on superiority to lamivudine, with a single-mutation resistance pathway giving 25.1% resistance at two years, a 12.9% rate of severe creatine kinase elevation, and a combination trial subsequently stopped for peripheral neuropathy — in a field where entecavir had been licensed since March 2005 with 1.2% resistance at five years. The withdrawal is the field completing an arithmetic it could have done at approval.
Source
Drugs@FDA application records NDA 022011 and NDA 022154 (TYZEKA, Novartis), marketing status Discontinued
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 randomised outcome evidence in hepatitis B still belongs to lamivudine
In plain words
Telbivudine was never randomised against placebo for deaths, cancers or liver failure. The one trial that measured those things tested lamivudine — the drug telbivudine was compared against.
What was measured
That telbivudine reduces cancer or decompensation — inferred through two links, neither of which measured that outcome for this drug
Effect estimate
No reviewed effect estimate exists for this record.
Limits
See the technical detail.
From the source
GLOBE measured a composite of viral load, HBeAg status and liver enzymes at one and two years, with a histologic secondary endpoint. The only randomised placebo-controlled hepatitis B trial with clinical outcomes randomised 651 patients with cirrhosis or advanced fibrosis to lamivudine or placebo and found disease progression in 7.8% against 17.7% and hepatocellular carcinoma in 3.9% against 7.4%. The chain of inference for telbivudine therefore runs: lamivudine beats placebo on hard outcomes, telbivudine beats lamivudine on a surrogate composite, therefore telbivudine improves hard outcomes. Each link is real and the chain has never been tested end to end — and the middle link is undermined by the resistance data, since 25.1% of patients had escaped the drug by the point at which the lamivudine outcome trial was still accruing events.
Source
Liaw YF et al., N Engl J Med 2004;351:1521-1531; Lai CL et al., N Engl J Med 2007;357:2576-2588
Role in the trial
Not matched to a registered study
Identity check
no open identity hold
Audit mark
contested
Review state
Written into the record, not signed off as a reviewed claim

Where else this substance is registered

FDA substance identifier (UNII)
2OC4HKD3SF
CAS registry number
3424-98-4
PubChem compound
159269
ChEMBL
CHEMBL374731
ChEBI
63624
WHO international nonproprietary name list entry
8296
RxNorm concept
474128
EMA substance identifier
100000089257
DrugBank
DB01265

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What is missing or unclearRead from sources, not yet reviewed

How this medicine reached us

Kept near the foot of the page. A historical event moves up only when it changes something about this substance today.

  1. Withdrawn, in European Union; no reason is published (EMA Medicine.csv)

What the approval register records

  • 2 approved applications cover products containing this substance. The earliest was NDA022011, approved 20061025 to NOVARTIS.

    Drugs@FDA application register · NDA022011 · read 2026-08-29

  • Marketing status on the register: discontinued.

    Drugs@FDA application register · NDA022011 · read 2026-08-29

What is missing or unclearRead from sources, not yet reviewed

What to learn next

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  • Felt, measured, or meaningful — found nothing in the sources checked.
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  • Other ways to the same goal — found nothing in the sources checked.
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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 L-nucleoside that beat lamivudine in a 1,370-patient double-blind trial — 63% against 48% therapeutic response and 25.1% against 39.5% resistance at two years — while entecavir, approved a year earlier, was already reaching 1.2% resistance at five; its combination trial with peginterferon was stopped early after peripheral neuropathy in 7 of 50 patients, and both United States presentations are now discontinued.

Recorded evidence blocks (7)

55 registered trials of Telbivudine — at which phases?


Registered studies posting no result
46 of 55

55 registered studies of Telbivudine: 28 phase4, 14 phase3, 5 na, 5 phase2, 3 na or unstated, 2 phase1. CLINICALTRIALS_SNAPSHOT · 2026-09-01

97 with a PubMed record

Show the evidence
  • phase4
    28
  • phase3
    14
  • na
    5
  • phase2
    5
  • na or unstated
    3
  • phase1
    2
4 more recorded rows
  • completed
    28
  • unknown
    16
  • withdrawn
    6
  • terminated
    5

recorded 2026-09-01 · last checked 2026-09-04

10 of Telbivudine's trials stopped: safety, futility/efficacy, accrual/recruitment, funding/business, other?


safety (1), futility/efficacy (1), accrual/recruitment (3), funding/business (1) and other (4): Telbivudine's stop wording, clustered. CLINICALTRIALS_SNAPSHOT · 2026-09-01

"The study was not completed as planned and was terminated early with agreement from the European Medicines Agency (EMEA)"; 10 of 55 registered studies

Show the evidence

Trial

  • NCT00376259
    terminated; "The study was not completed as planned and was terminated early with agreement from the European Medicines Agency (EMEA)"
  • NCT00409019
    withdrawn; "Study cancelled: Withdrawn before enrollment of any participants"
  • NCT00412750
    terminated; "Enrollment stopped for safety issues"
  • NCT00606099
    withdrawn; "study was cancelled"
  • NCT00710216
    withdrawn; "Sponsor withdraw"
  • NCT01005238
    terminated; "unsufficient patient recruitment"
4 further recorded trials
  • NCT01260610
    withdrawn; "lack of funds"
  • NCT02049736
    withdrawn; "unable to recruit patients"
  • NCT02058108
    terminated; "Study terminated on the recommendation of an independent Data Monitoring Committee (DMC) subsequent to an interim efficacy analysis for futility.\]"
  • NCT02894554
    terminated; "clinical myalgia"

recorded 2026-09-01 · last checked 2026-09-04

Human studies of Telbivudine used Telbivudine 600mg — over how long?


Human studies of Telbivudine used "Telbivudine 600mg". ClinicalTrials.gov · 2026-09-01

Show the evidence
  • human NCT03468907
    Telbivudine 600mg

recorded 2026-09-01 · last checked 2026-09-04

Which 19 trials of Telbivudine posted no result?


Posted no result
19 of 19 completed trials
Registrations
NCT00124241, NCT00115245, NCT00132652, NCT00131742, NCT00128544 and NCT00467545, and 13 more
Completion dates
oldest 2005-11; newest 2018-05-31
Show the evidence

Trial

  • NCT00124241
    2005-11
  • NCT00115245
    2006-08
  • NCT00132652
    2006-12
  • NCT00131742
    2007-01
  • NCT00128544
    2007-05
  • NCT00467545
    2009-09
13 further recorded trials
  • NCT00646503
    2009-09
  • NCT00640588
    2009-12
  • NCT00804622
    2010-03
  • NCT00781105
    2010-09-16
  • NCT01480492
    2011-10
  • NCT00962533
    2012-08
  • NCT01743079
    2013-07
  • NCT01788371
    2013-07
  • NCT01637844
    2014-10
  • NCT01595685
    2014-12
  • NCT02447705
    2017-01-31
  • NCT03468907
    2017-12-31
  • NCT03778567
    2018-05-31

At the median, Telbivudine's trials enrolled 110.5 people — anything larger?


Median enrolment
110.5
Largest enrolment
2200
Registered trials counted
52

What do 709 spontaneous reports say about Telbivudine — 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.

Telbivudine appears in spontaneous reports to regulators. Across the 10 most-reported reaction terms, 709 reaction mentions were counted: blood creatine phosphokinase increased 165; myalgia 110; drug resistance 79; muscular weakness 65. FAERS via Open Targets · CHEMBL374731 · 2026-06-24

Show the evidence
  • blood creatine phosphokinase increased
    165
  • myalgia
    110
  • drug resistance
    79
  • muscular weakness
    65
  • fatigue
    62
  • hypoaesthesia
    56
4 more recorded rows
  • pain in extremity
    46
  • rhabdomyolysis
    44
  • asthenia
    44
  • gait disturbance
    38

recorded 2026-06-24 · last checked 2026-09-04

Where do the label and the trials disagree about Telbivudine?


"withdrawn" against "approved": withdrawal status vs register status for Telbivudine.

EMA_MEDICINE_REGISTER, Drugs@FDA; 1 recorded pair

Show the evidence
  • EMA_MEDICINE_REGISTER EMEA/H/C/000713
    withdrawn; 2026-09-04
  • Drugs@FDA NDA022011
    approved; 2026-08-28
Where it is registered

Where it’s registered

Withdrawn, in European Union; no reason is published (EMA Medicine.csv)

Identifiers, relations and other names

The exact record

ChEMBL id
CHEMBL374731
PubChem CID
159269
CAS number
3424-98-4
RxCUI
474128
InChIKey
IQFYYKKMVGJFEH-CSMHCCOUSA-N
Also called
2'-deoxy-l-thymidine, Telbivudina, ldt, 2,4(1H,3H)-PYRIMIDINEDIONE,1-(2-DEOXY-.BETA.-L-ERYTHRO-PENTOFURANOSYL)-5-METHYL-, TELBIVUDINE [EMA EPAR], TELBIVUDINE [MART.], TELBIVUDINE [MI], TELBIVUDINE [ORANGE BOOK], TELBIVUDINE [USAN]
Development code
LDT-600, LDT600, NV-02B
Trade name
Sebivo, Tyzeka
Sources (6)

Sources

ChEMBL 37 — CC BY-SA 3.0 Unported · ChEMBL ATC CC BY-SA · 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

How these records are assembled · Which registers were checked

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  • public claims reviewed: 0 reviewed claim(s); drafts are never rendered
  • source coverage passed: 6 source rows
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