Immune Peptide Research

Thymosin Alpha-1: Thymalfasin Research Data

A conservative review of thymosin alpha-1: its chemistry and thymus origin, the immune-signalling data, the large and largely negative clinical trials, and where regulators stand in 2026.

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Fact-checked · Reviewed by Remy Research Editorial Board
Update History ▾
October 6, 2026: Initial publication, built from a source-by-source check of the thymosin alpha-1 literature, including the corrected TESTS sepsis results, FDA's 2024 compounding review and current registration records.
Research-use-only framing applied throughout in line with Remy editorial standards.
TL;DR — Research Summary

Thymosin alpha-1 is a 28-amino-acid immune peptide, sold as the drug thymalfasin (Zadaxin) in China, Italy and other countries, whose largest modern trials have been negative. Cell and mouse studies link it to dendritic-cell activation through Toll-like receptor signalling.[1][2] But the 1,106-patient TESTS sepsis trial found no reduction in 28-day mortality, and a 508-patient pancreatitis trial, a US hepatitis B phase III trial and a European hepatitis C trial also missed their primary endpoints.[3][4][5][6]

It is not FDA-approved: in December 2024 FDA's compounding advisory committee voted 4–17 against listing it, and FDA found a lack of evidence of effectiveness for every use it reviewed.[7][8] Material supplied by Remy Research is for in-vitro laboratory research only — not for human or veterinary use.

Compliance note: this page is a research review, not a treatment guide. It does not provide human-use dosing, therapeutic recommendations, or any clinical-use instructions, and should be read in the same non-therapeutic frame required across Remy's research content.

What Is Thymosin Alpha-1?

Thymosin alpha-1 (Tα1) is a 28-amino-acid peptide acetylated at its N-terminus; its drug name is thymalfasin. PubChem lists it as C129H215N33O55, with a molecular weight of about 3,108 g/mol, CAS number 62304-98-7, and PubChem CID 16130571.[9]

Its sequence is identical to residues 2–29 of prothymosin α, a natural protein.[10] A 1984 study found prothymosin α, not free Tα1, to be the main form in rat thymus, and proposed that Tα1 is produced from it during extraction, so whether free Tα1 circulates naturally is still debated.[11]

Origin and a Name It Shares

Allan Goldstein's group isolated and sequenced Tα1 from calf thymus in 1977, as one of several peptides in a preparation called thymosin fraction 5.[12] Thymosin beta-4 was sequenced from the same fraction in 1981.[13]

That shared origin is the only link between the two. Thymosin alpha-1 and thymosin beta-4 — the parent of TB-500 — come from different genes, differ in size and biology, and have different regulatory and anti-doping status. The drug version of Tα1 was later developed and marketed by SciClone as Zadaxin.[8]

Proposed Mechanisms and the Evidence Behind Each

Thymosin Alpha-1 — Proposed Mechanisms and Evidence
Proposed mechanism What was reported Evidence type
TLR signalling Activated dendritic cells through Toll-like receptor and MyD88 signalling; protected mice against fungal infection In vitro, animal
Antiviral sensing Protected mice against cytomegalovirus through TLR9, MyD88 and IRF7 signalling Animal
Tolerance (IDO) Induced the enzyme IDO in dendritic cells, promoting regulatory T cells In vitro, animal
Human biomarkers Changes in immune markers such as monocyte HLA-DR in some trials; results inconsistent Human surrogate markers

The mechanistic work comes mostly from a few groups, many in Perugia and Rome, and combines innate immune activation with a tolerance-promoting arm.[1][2][14] No specific high-affinity receptor has been established.

Clinical Evidence: The Large Trials

1. Sepsis

The TESTS trial randomised 1,106 adults with sepsis across 22 Chinese centres, double-blind and placebo-controlled. It found no reduction in 28-day mortality: 23.4% against 24.1%, with a corrected hazard ratio of 0.97; the PubMed abstract still shows the figures from before a published correction.[3][15] An earlier single-blind trial of 361 patients had a borderline, non-significant result, and a 2025 meta-analysis found no significant benefit when only high-quality or multicentre trials were pooled.[16][17]

2. Pancreatitis

In a 508-patient double-blind trial in predicted severe necrotising pancreatitis, Tα1 did not reduce infected pancreatic necrosis.[4]

3. Hepatitis B and C

A US multicentre, double-blind phase III trial in chronic hepatitis B did not confirm efficacy, although a smaller randomised Taiwanese trial reported higher delayed virological response.[5][18] In a 552-patient trial adding Tα1 to peginterferon and ribavirin in hepatitis C, the primary endpoint was not met.[6]

4. Melanoma and COVID-19

In a 488-patient randomised melanoma study, arms with Tα1 had more tumour responses, but survival differences were not statistically significant.[19] COVID-19 data are mixed: a small retrospective Wuhan series reported lower mortality, a larger propensity-matched cohort found no difference, and a small US randomised pilot found no significant clinical benefit.[20][21][22]

Across these studies, positive results come mostly from smaller, open-label or retrospective work, largely from China and Italy, and several trials had SciClone funding or author ties. FDA's 2024 review found a lack of evidence of effectiveness for every use it evaluated.[8]

What Has Been Published on Safety

Regulatory Status in 2026

Where thymosin alpha-1 stands as of October 6, 2026.
  • Approved markets. China approves thymalfasin for chronic hepatitis B and as a vaccine-response enhancer in immunocompromised people, with generic versions available. Italy authorises Zadaxin as an influenza-vaccine adjuvant in immunocompromised people.[23][24]
  • United States. Not approved. It holds four orphan designations, none leading to approval.[25] It was removed from Category 2 in September 2024 after its nomination was withdrawn, and in December 2024 the advisory committee voted 4–17 against adding either form to the 503A Bulks List.[26][7] Some 2026 reports say it returned to Category 1, but FDA's May 2026 list does not show it in any category.[27]
  • European Union. There is no EU-wide authorisation; an EU orphan designation for liver cancer remains active, which is not a marketing authorisation.[24]
  • United Arab Emirates. No UAE registration could be verified. A randomised, placebo-controlled trial of Tα1 in IVF implantation failure is recruiting in Abu Dhabi, which makes it investigational there, not registered.[28]
  • Sport. Thymosin alpha-1 is not named on WADA's 2026 or 2027 Prohibited List, and because thymalfasin holds national approvals, the S0 clause does not obviously apply. Thymosin beta-4 and TB-500, by contrast, are prohibited by name.[29]

What the Thymosin Alpha-1 Literature Does Not Yet Give You

With 889 PubMed records and 66 registered studies, Tα1 is far better studied than most research peptides — which makes the null results of its largest trials the most important part of the record.[30]

Where Thymosin Alpha-1 Fits in an RUO Research Catalog

For research use, thymosin alpha-1 belongs with the immune-signalling peptide research tools: a defined 28-residue peptide for cell-culture and animal-model work on dendritic-cell activation and Toll-like receptor signalling. Remy Research lists the Genovare Thymosin Alpha-1 25mg AQ pen, supplied for in-vitro laboratory research only. It is not framed for human use, veterinary use or treatment.

For researchers reading this page as a starting point, the most useful adjacent references on this site are the TB-500 and thymosin beta-4 review, the KPV review, the COA and HPLC purity guide, and the Dubai legality brief.

Our Research Standards

This article prioritizes randomised trials, regulatory reviews and primary literature, and reports null primary endpoints alongside positive findings. Where evidence is weak, we say so directly. No therapeutic, human-use, or veterinary-use claim is made here. Read our editorial policy →

RP
Editorial Review

Editorial Board, Remy Research

The Remy Research Editorial Board reviews Remy's peptide research library, with a focus on analytical verification, clinical-trial interpretation, and compliance-safe scientific communication.

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Thymosin Alpha-1 Research FAQ

What is thymosin alpha-1?

A 28-amino-acid peptide, acetylated at its N-terminus, identical to residues 2–29 of the natural protein prothymosin α. Allan Goldstein's group isolated it from calf thymus in 1977. Its drug name is thymalfasin, sold as Zadaxin in some countries.[12][10]

Is thymosin alpha-1 FDA-approved?

No. It holds four US orphan designations, none of which led to approval. In December 2024 FDA's compounding advisory committee voted 4–17 against adding it to the 503A Bulks List, and FDA's May 2026 list does not include it in any category.[25][7][27]

Where is thymosin alpha-1 approved as a medicine?

Current records confirm China, for chronic hepatitis B and as a vaccine-response enhancer in immunocompromised people, and Italy, as an influenza-vaccine adjuvant in immunocompromised people. It is not approved in the US or EU-wide.[23][24]

How is thymosin alpha-1 different from thymosin beta-4 and TB-500?

They are different molecules from different genes that share a name only because both were first isolated from the same thymus extract. Thymosin alpha-1 has 28 residues and is studied for immune signalling; thymosin beta-4 has 43 residues and binds actin. WADA prohibits thymosin beta-4 and TB-500 by name but does not name thymosin alpha-1.[13][29]

Does thymosin alpha-1 help in sepsis?

The largest trial says no. TESTS, with 1,106 adults in 22 Chinese centres, found no reduction in 28-day mortality: 23.4% against 24.1%. Pooled analyses show a benefit only when lower-quality trials are included.[3][17]

What does the COVID-19 evidence show?

It is mixed and of low quality: a small retrospective series reported lower mortality, a larger propensity-matched cohort found no difference, and a small US randomised pilot found no significant clinical benefit.[20][21][22]

Is thymosin alpha-1 banned in sport?

It is not named on WADA's 2026 or 2027 Prohibited List, and because thymalfasin holds national approvals, the S0 clause does not obviously apply; that is not an official ruling. Thymosin beta-4 and TB-500 are prohibited by name.[29]

What side effects have studies reported?

Trials and labels mainly describe injection-site discomfort and transient liver-enzyme rises in hepatitis B. In TESTS, a prespecified subgroup under 60 had higher mortality on Tα1, which was not significant after adjustment. FDA flagged immunogenicity and impurity concerns for compounded material.[8][3]

Sources

  1. Romani L, Bistoni F, Gaziano R, et al. Thymosin alpha 1 activates dendritic cells for antifungal Th1 resistance through toll-like receptor signaling. Blood. 2004;103(11):4232-4239. doi: 10.1182/blood-2003-11-4036 · PMID: 14982877 ↩
  2. Bozza S, Gaziano R, Bonifazi P, et al. Thymosin alpha1 activates the TLR9/MyD88/IRF7-dependent murine cytomegalovirus sensing for induction of anti-viral responses in vivo. Int Immunol. 2007;19(11):1261-1270. doi: 10.1093/intimm/dxm097 · PMID: 17804687 ↩
  3. Wu J, Pei F, Zhou L, et al. The efficacy and safety of thymosin α1 for sepsis (TESTS): multicentre, double blinded, randomised, placebo controlled, phase 3 trial. BMJ. 2025;388:e082583. doi: 10.1136/bmj-2024-082583 · PMID: 39814420 ↩
  4. Ke L, Zhou J, Mao W, et al. Immune enhancement in patients with predicted severe acute necrotising pancreatitis: a multicentre double-blind randomised controlled trial. Intensive Care Med. 2022;48(7):899-909. doi: 10.1007/s00134-022-06745-7 · PMID: 35713670 ↩
  5. Mutchnick MG, Lindsay KL, Schiff ER, et al. Thymosin alpha1 treatment of chronic hepatitis B: results of a phase III multicentre, randomized, double-blind and placebo-controlled study. J Viral Hepat. 1999;6(5):397-403. doi: 10.1046/j.1365-2893.1999.00181.x · PMID: 10607256 ↩
  6. Ciancio A, Andreone P, Kaiser S, et al. Thymosin alpha-1 with peginterferon alfa-2a/ribavirin for chronic hepatitis C not responsive to IFN/ribavirin: an adjuvant role? J Viral Hepat. 2012;19 Suppl 1:52-59. doi: 10.1111/j.1365-2893.2011.01524.x · PMID: 22233415 ↩
  7. U.S. Food and Drug Administration. Minutes of the December 4, 2024 Pharmacy Compounding Advisory Committee meeting (thymosin alpha-1 votes 4 yes, 17 no for each form). fda.gov/media/185642 ↩
  8. U.S. Food and Drug Administration. Briefing document on thymosin alpha-1 (free base) and thymosin alpha-1 acetate for the December 4, 2024 Pharmacy Compounding Advisory Committee meeting. fda.gov/media/183820 ↩
  9. National Center for Biotechnology Information. PubChem Compound Summary for CID 16130571, Thymalfasin. pubchem.ncbi.nlm.nih.gov/compound/16130571 ↩
  10. UniProt. P06454 — Prothymosin alpha (PTMA_HUMAN); residues 2–29 form thymosin alpha-1. uniprot.org ↩
  11. Haritos AA, Goodall GJ, Horecker BL. Prothymosin alpha: isolation and properties of the major immunoreactive form of thymosin alpha 1 in rat thymus. Proc Natl Acad Sci U S A. 1984;81(4):1008-1011. doi: 10.1073/pnas.81.4.1008 · PMID: 6583693 ↩
  12. Goldstein AL, Low TL, McAdoo M, et al. Thymosin alpha1: isolation and sequence analysis of an immunologically active thymic polypeptide. Proc Natl Acad Sci U S A. 1977;74(2):725-729. doi: 10.1073/pnas.74.2.725 · PMID: 265536 ↩
  13. Low TL, Hu SK, Goldstein AL. Complete amino acid sequence of bovine thymosin beta 4: a thymic hormone that induces terminal deoxynucleotidyl transferase activity in thymocyte populations. Proc Natl Acad Sci U S A. 1981;78(2):1162-1166. doi: 10.1073/pnas.78.2.1162 · PMID: 6940133 ↩
  14. Romani L, Bistoni F, Perruccio K, et al. Thymosin alpha1 activates dendritic cell tryptophan catabolism and establishes a regulatory environment for balance of inflammation and tolerance. Blood. 2006;108(7):2265-2274. doi: 10.1182/blood-2006-02-004762 · PMID: 16741252 ↩
  15. BMJ. Correction: The efficacy and safety of thymosin α1 for sepsis (TESTS): multicentre, double blinded, randomised, placebo controlled, phase 3 trial. BMJ. 2025;389:r1098. doi: 10.1136/bmj.r1098 · PMID: 40447307 ↩
  16. Wu J, Zhou L, Liu J, et al. The efficacy of thymosin alpha 1 for severe sepsis (ETASS): a multicenter, single-blind, randomized and controlled trial. Crit Care. 2013;17(1):R8. doi: 10.1186/cc11932 · PMID: 23327199 ↩
  17. Gu B, Zhou Y, Nie Y, et al. Efficacy of thymosin α1 for sepsis: a systematic review and meta-analysis of randomized controlled trials. Front Cell Infect Microbiol. 2025;15:1673959. doi: 10.3389/fcimb.2025.1673959 · PMID: 40969554 ↩
  18. Chien RN, Liaw YF, Chen TC, et al. Efficacy of thymosin alpha1 in patients with chronic hepatitis B: a randomized, controlled trial. Hepatology. 1998;27(5):1383-1387. doi: 10.1002/hep.510270527 · PMID: 9581695 ↩
  19. Maio M, Mackiewicz A, Testori A, et al. Large randomized study of thymosin alpha 1, interferon alfa, or both in combination with dacarbazine in patients with metastatic melanoma. J Clin Oncol. 2010;28(10):1780-1787. doi: 10.1200/JCO.2009.25.5208 · PMID: 20194853 ↩
  20. Liu Y, Pan Y, Hu Z, et al. Thymosin Alpha 1 Reduces the Mortality of Severe Coronavirus Disease 2019 by Restoration of Lymphocytopenia and Reversion of Exhausted T Cells. Clin Infect Dis. 2020;71(16):2150-2157. doi: 10.1093/cid/ciaa630 · PMID: 32442287 ↩
  21. Sun Q, Xie J, Zheng R, et al. The effect of thymosin α1 on mortality of critical COVID-19 patients: A multicenter retrospective study. Int Immunopharmacol. 2021;90:107143. doi: 10.1016/j.intimp.2020.107143 · PMID: 33208294 ↩
  22. Shehadeh F, Benitez G, Mylona EK, et al. A Pilot Trial of Thymalfasin (Thymosin-α-1) to Treat Hospitalized Patients With Hypoxemia and Lymphocytopenia Due to Coronavirus Disease 2019 Infection. J Infect Dis. 2023;227(2):226-235. doi: 10.1093/infdis/jiac362 · PMID: 36056913 ↩
  23. Thymalfasin for injection (approval H20193180): Chinese package insert, approved for chronic hepatitis B and as a vaccine-response enhancer in immunocompromised patients. package insert ↩
  24. European Medicines Agency. Orphan designation EU/3/02/110, thymalfasin for hepatocellular carcinoma (2002), noting national authorisation in Italy as an influenza-vaccine adjuvant. ema.europa.eu ↩
  25. U.S. Food and Drug Administration, Office of Orphan Products Development. Orphan designation of thymalfasin for chronic active hepatitis B (May 3, 1991; designated, not approved); further designations in 1998, 2000 and 2006. accessdata.fda.gov ↩
  26. U.S. Food and Drug Administration. Certain bulk drug substances for use in compounding that may present significant safety risks ("Thymosin-alpha 1 (Ta1)" listed under "nominated but withdrawn"; page modified April 22, 2026). fda.gov ↩
  27. U.S. Food and Drug Administration. Bulk drug substances nominated for use in compounding under section 503A: Categories 1–3 (updated May 14, 2026; thymosin alpha-1 not listed). fda.gov/media/94155 ↩
  28. ClinicalTrials.gov NCT07675980. Thymosin-α1 for recurrent implantation failure after transfer of PGT-A tested embryos (Abu Dhabi; randomized, placebo-controlled; recruiting). clinicaltrials.gov ↩
  29. World Anti-Doping Agency. 2027 Prohibited List: thymosin alpha-1 is not named; thymosin-β4 and its derivatives such as TB-500 are prohibited under S2. wada-ama.org ↩
  30. PubMed title/abstract search for thymosin alpha-1, thymalfasin or Zadaxin, run October 6, 2026 (889 records); ClinicalTrials.gov lists 66 studies. pubmed.ncbi.nlm.nih.gov ↩

For catalog details, see the Genovare Thymosin Alpha-1 25mg AQ pen. For compliance context, continue to the Dubai legality brief and the research standards page.

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