Thymosin α1

BApproved outside US/EU (Zadaxin)thymalfasinZadaxinTα1
In one paragraphThymosin α1 is a 28-amino-acid peptide from the thymus that nudges T-cells and dendritic cells toward a stronger antiviral response. It has been sold as Zadaxin for hepatitis B and as an immune adjunct in China, Italy and some thirty other countries since the 1990s, but the largest trial ever run on it — 1,106 adults with sepsis, published in the BMJ in January 2025 — found no reduction in 28-day mortality (23.4% versus 24.1%). It is not approved in the US, EU-wide or UK.
Schematic 3D structure of Thymosin α1
28 residues · acetylated, largely unstructured in solution · schematic
Overall gradeB Probable
Human trials20+ RCTs
Outcomes graded5
Last reviewed3 September 2026
EvidenceWhat it isHow it worksUnknownsRegulationQuestionsReferences

What the human research shows

A rare case of a peptide with a large, well-run, negative trial. The B reflects decades of moderate-quality positive RCTs in hepatitis and as a vaccine adjunct, cut down by TESTS, which is the highest-quality evidence on the compound and found nothing. Earlier meta-analyses that showed benefit in sepsis were built on trials smaller than this one.

OutcomeGradeEffect sizeHuman studiesWhere the evidence comes from
Sepsis mortalityAEstablishedNot measurable1 large phase 3 RCT + earlier smaller RCTsTESTS, 1,106 adults in 22 Chinese ICUs, twice-daily injections for 7 days: 28-day mortality 23.4% versus 24.1% on placebo (hazard ratio 0.97, 95% CI 0.76–1.24). No secondary or safety outcome differed. Earlier smaller trials that suggested benefit are superseded.1
Chronic hepatitis B (viral response)BProbableSmall10+ RCTs, mostly smallTrials from the 1990s–2000s show modest increases in sustained response, alone or with interferon; heterogeneous quality. The basis for the Zadaxin approvals.2
Vaccine response in the elderly and dialysis patientsBProbableSmallSeveral RCTsImproved seroconversion to influenza and hepatitis B vaccines in older adults and haemodialysis patients in randomised studies; effect sizes moderate, trials small.2
COVID-19 outcomesCWeakSmallObservational + small RCTsChinese observational cohorts and small randomised studies reported lower mortality in severe COVID-19; confounded and never confirmed in a large trial.3
SafetyadverseAEstablishedNot measurableTESTS + decades of useInjection-site reactions; no signal for serious harm in TESTS or in long clinical use. Subgroup findings in TESTS (worse in under-60s, better in diabetics) are hypothesis-generating only.1
AMultiple good human trials, consistentBSome human trials, mostly consistentCFew or weak human studiesDAnimal or anecdotal onlyeffect size · red = adverse

Literature searched to 3 September 2026. Human studies only; animal and cell work informs the mechanism section and nothing else.

What it is

A naturally occurring acetylated peptide, N-terminal fragment of prothymosin α, first isolated from calf thymus in 1977. The synthetic drug (thymalfasin, Zadaxin) was developed by SciClone and is approved in China — its largest market by far — plus Italy and a scattering of countries in Asia, Latin America and the Middle East.

In the United States it has orphan designation for several indications but no approval; in the EU it is authorised only in Italy under national rules. The 'research' vials sold online are unrelated to the licensed product.

How it is thought to work

Acts through Toll-like receptors on dendritic cells and enhances T-cell maturation and function, tilting the immune response toward antiviral and antitumour activity while dampening excessive inflammation. In sepsis the hypothesis was that it would reverse immune paralysis; TESTS did not bear it out.

What is still unknown

  • Whether any subgroup in sepsis genuinely benefits — the trial's age and diabetes signals need their own trials.
  • Its value as a hepatitis B adjunct in the era of modern antivirals.

Regulatory status

European Union
Authorised in Italy only

Zadaxin is nationally authorised in Italy; no EU-wide marketing authorisation. Elsewhere in the EU it is an unauthorised medicine.

United States
Not approved; compounding withdrawn

Orphan designations but no approval. Its 503A compounding nomination is listed as withdrawn (April 2026).

United Kingdom
Not licensed

No MHRA licence; unlicensed medicine when supplied for human use.

Australia
Not registered

Not on the ARTG; prescription-only substance.

Canada
Not authorised

No DIN.

Sport (WADA)
Not on the list

Approved in several countries, so S0 does not apply; not named in any section.

Questions people actually ask

Is thymosin alpha 1 approved?
In China, Italy and roughly thirty other countries, yes, as Zadaxin for hepatitis B and as an immune adjunct. Not in the US, not EU-wide, not in the UK, Australia or Canada.
Does thymosin alpha 1 help in sepsis?
The best evidence says no. TESTS, a 1,106-person double-blind phase 3 trial published in the BMJ in 2025, found 28-day mortality of 23.4% with the drug and 24.1% with placebo. Earlier meta-analyses suggesting benefit rested on smaller trials.
Is it the same as TB-500?
No. Thymosin α1 and thymosin β4 are different peptides with different biology. TB-500 is a fragment of thymosin β4, has no approvals anywhere, and is prohibited in sport; thymosin α1 is an approved immune drug in several countries and not on the WADA list.

One page per claimed effect

References

  1. 1
  2. 2
    Thymalfasin (Zadaxin) clinical overview: hepatitis B and vaccine-adjuvant randomised trials.Multiple journals, 1996–2015Heterogeneous, mostly small RCTs.
  3. 3
    Efficacy of thymosin α1 for sepsis: a systematic review and meta-analysis of randomized controlled trials.Front Cell Infect Microbiol, 2025Includes TESTS; earlier pooled estimates were driven by small trials.

Change log

  • 2026-09-03Initial publication, led by the TESTS trial.