Skip to content
Calculator
Guide

Thymosin alpha-1: approved abroad, gray here, and the immune evidence

Last updated: October 3, 2026 · 7 min read · By the Grey Peptides Editorial Board

A hospital vital signs monitor
Photo by CARLOSCRUZ ARTEGRAFIA on Pexels
Grey Peptides
Grey Peptides Editorial Board
Every status on this page carries the date it was checked. How we work
Key takeaways
  • Thymosin alpha-1 is approved as Zadaxin in more than 35 countries, mainly for chronic hepatitis B, but not in the US.
  • Its largest and most rigorous trial, in 1,106 people with sepsis, found no survival benefit.
  • In 2024, FDA's compounding advisers voted 4 to 17 against adding it to the list of substances pharmacies may compound; FDA cites immunogenicity and impurity concerns.
  • It is a completely different molecule from TB-500, despite the shared 'thymosin' name, and the two should never be treated as interchangeable.

What thymosin alpha-1 is

Thymosin alpha-1 is a 28-amino-acid peptide originally isolated from thymus tissue; its drug form is called thymalfasin. It is approved in more than 35 countries, including Italy, China and much of Asia, as Zadaxin, for chronic hepatitis B and C and as an immune enhancer, and it holds FDA orphan designations for several conditions but no US marketing approval 1. A 2018 review notes that blood levels are lower than normal in hepatitis B, sepsis and several autoimmune conditions, while normal baseline levels and the best dose and schedule remain unsettled (review) 2.

The hepatitis trials: the basis of its approvals

Thymosin alpha-1's foreign approvals rest mainly on hepatitis. In a 1998 trial of 98 patients with chronic hepatitis B, complete virological response at 18 months was 40.6% after 26 weeks of treatment, 26.5% after 52 weeks and 9.4% in untreated controls; the groups had looked similar at the end of therapy (randomised trial) 3. Added to interferon in 98 HBeAg-positive patients, HBeAg loss at 72 weeks was 45.8% against 28.0% on placebo, a difference that missed statistical significance (randomised trial) 4. In hepatitis C, added to interferon in 109 patients, end-of-treatment response was 37.1% against 16.2% on interferon alone (randomised trial) 5.

These trials are decades old, small and run alongside interferon-era treatments. Treatment for both diseases has changed greatly since, so these results cannot be read as evidence for using thymosin alpha-1 today in place of current therapy.

Sepsis: a large trial and a clear null

Smaller Chinese studies had suggested benefits in sepsis: a pooled review of five trials with 198 patients reported better immune markers, lower severity scores and shorter ventilation (review) 6. The definitive test was TESTS, which randomised 1,106 adults with sepsis across 22 Chinese centres to thymosin alpha-1 or placebo every 12 hours for seven days. Twenty-eight-day mortality was 23.4% against 24.1% (hazard ratio 0.99), and no secondary or safety outcome differed (randomised trial) 7. Prespecified subgroups pointed in opposite directions, a hazard ratio of 1.67 in patients under 60 and 0.58 in those with diabetes 7; subgroup results like these generate hypotheses for new trials rather than establishing who benefits.

That is the most important result in the thymosin alpha-1 literature: a large, placebo-controlled trial that did not confirm the promise of smaller studies.

ConditionBest trialResult
SepsisTESTS, 1,106 adults, 22 Chinese centres (2025)No mortality benefit: 23.4% vs 24.1% at 28 days
Chronic hepatitis B98 patients, three arms (1998)Complete response at 18 months 40.6% (26 weeks) vs 9.4% control
Hepatitis B with interferon98 patients, double-blind (2006)HBeAg loss 45.8% vs 28.0%, not significant
Hepatitis C with interferon109 patients (1998)End-of-treatment response 37.1% vs 16.2% on interferon alone
COVID-19Meta-analysis of 8 studies (2023)Lower mortality pooled, with 84% heterogeneity

COVID-19 and other immune uses

During the pandemic, thymosin alpha-1 was widely used in China. A 2023 meta-analysis of eight studies in moderate to critical COVID-19 found lower mortality (risk ratio 0.59) but with 84% heterogeneity, no effect on ventilation or length of stay, and an effect that varied with study size (meta-analysis) 8. A retrospective study of 275 patients found no difference in T-cell recovery and slower viral clearance in treated patients (observational study) 9, and a small randomised trial of 49 hospitalised patients found more frequent recovery that did not reach significance (randomised trial) 10.

Other uses remain exploratory. In dialysis patients, adding it to an H1N1 vaccine improved antibody responses in a pilot study (randomised trial) 11. In 20 people with HIV and poor CD4 recovery, the CD4 share rose but the count did not change significantly (human study) 12. In cancer, single-arm studies combine it with chemotherapy or immunotherapy, which makes its own contribution impossible to isolate (single-arm trials) 13 14.

The US position, as of October 3, 2026

Thymosin alpha-1 is not FDA-approved 1. Its route to US use through compounding pharmacies has been blocked by the advisory process. The nomination to add it to the 503A bulks list, the list of substances pharmacies may compound, was withdrawn by its nominator, but FDA chose to present it to its Pharmacy Compounding Advisory Committee anyway 15. On December 4, 2024, the committee voted 4 in favour and 17 against adding thymosin alpha-1 to the list, a non-binding recommendation 16. FDA's briefing raised a lack of characterisation data for impurities and aggregates and the potential for immunogenicity 15.

FDA's page of bulk substances that may present significant safety risks says compounded thymosin alpha-1 may pose significant immunogenicity risk for certain routes, may have impurity and characterisation complexities, and that safety information is inadequate to understand the extent of any safety issues 17. It is not on Category 2, which it left in 2024 when the nomination was withdrawn, and it was not among the peptides FDA removed from Category 2 and sent to advisory review in 2026 17. Our PCAC hub covers the 2026 process.

What FDA's reviewers found

FDA's 2024 briefing for the committee set out its reasoning. Its chemistry review concluded that the free-base form was not well characterised, noting no certificate of analysis for it in the nomination, no information on impurity limits, and no data on aggregation when formulated for injection under the skin 18. It cited a reported half-life of 1.9 to 3 minutes 18, and noted that in hepatitis studies benefits were generally seen with interferon alongside 18. After the vote, the committee's federal report recorded that the agency was reviewing the recommendations 19. As of October 3, 2026 we found no final FDA decision placing thymosin alpha-1 on, or formally excluding it from, the 503A list.

Why the trials disagree

The thymosin alpha-1 literature shows a pattern common to many peptides: positive results in small, often single-country or open-label studies, and a null result in the one large, rigorous trial 7. Small trials are more likely to show chance findings and to be published when positive, and pooled analyses with high heterogeneity, such as the COVID-19 meta-analysis with 84% 8, can point in a direction that later trials do not confirm. That does not mean thymosin alpha-1 has no effect on the immune system; immune markers change in several studies 12. It means changes in markers have not translated into the outcomes that matter in the largest test.

Quality: why impurities matter for this peptide

FDA's concern about impurities is not abstract. A 2022 analysis using liquid chromatography and mass spectrometry separated and quantified 23 thymalfasin-related impurities in a pharmacopoeia reference standard and applied the method to three commercial materials; the main impurities included deamidated and other modified forms (laboratory study) 20. Our guide to how peptides are made explains why such near-copies can matter for immune reactions.

Not the same as TB-500

The shared word 'thymosin' causes constant confusion. Thymosin alpha-1 is an immune-modulating peptide with foreign approvals; thymosin beta-4, from which TB-500 is derived, is an unrelated protein involved in cell movement and tissue repair, with no approval anywhere. Our TB-500 entry covers that molecule, and our epitalon vs thymalin page covers thymalin, a Russian thymus extract, which is different again.

Sport

Thymosin alpha-1 is not named on the WADA list. Whether S0 applies is unsettled in our tracker because of its approvals outside the US 1. Tested athletes should seek a ruling from their anti-doping organisation before using it, and keep the written answer.

Questions to ask before using thymosin alpha-1

  • What condition is it for, and has it been tested in that condition in a large placebo-controlled trial? For sepsis, the large trial was negative.
  • Is the product an approved Zadaxin product from a country where it is licensed, or a research powder?
  • Has it been tested for impurities, given FDA's concerns?
  • Am I subject to anti-doping rules?

The bottom line

Thymosin alpha-1 has more human data than most peptides sold online, and real approvals abroad based on older hepatitis trials. But its largest modern trial, in sepsis, found no benefit, its COVID-19 evidence is inconsistent, and FDA's advisers voted against allowing it in compounding, citing immunogenicity and impurity concerns. In the US it remains unapproved, and the 2026 peptide changes did not alter that.

Frequently asked questions

Is thymosin alpha-1 FDA-approved?

No. It is approved as Zadaxin in more than 35 countries, mainly for chronic hepatitis B, but not in the US.

Does thymosin alpha-1 help sepsis?

The TESTS trial of 1,106 adults found 28-day mortality of 23.4% with thymosin alpha-1 and 24.1% with placebo, no meaningful difference.

Can US pharmacies compound thymosin alpha-1?

FDA's advisory committee voted 4 to 17 against adding it to the 503A bulks list in December 2024, and FDA lists immunogenicity and impurity concerns.

Is thymosin alpha-1 the same as TB-500?

No. TB-500 is derived from thymosin beta-4, an unrelated protein.

What is Zadaxin?

The brand name for thymalfasin, the drug form of thymosin alpha-1, approved in more than 35 countries.

Sources

  1. Grey Peptides encyclopedia entry for thymosin alpha-1 (approved in 35+ countries as Zadaxin; FDA orphan designations; not FDA-approved; WADA unsettled). Read October 3, 2026.
  2. Pica, F., et al. (2018). Serum thymosin alpha 1 levels in normal and pathological conditions. Expert Opin Biol Ther, 18(sup1), 13-21. PMID: 30063864
  3. Chien, R. N., et al. (1998). Efficacy of thymosin alpha1 in patients with chronic hepatitis B: a randomized, controlled trial. Hepatology, 27(5), 1383-7. PMID: 9581695
  4. Lim, S. G., et al. (2006). A randomized, placebo-controlled trial of thymosin-alpha1 and lymphoblastoid interferon for HBeAg-positive chronic hepatitis B. Antivir Ther, 11(2), 245-53. PMID: 16640105
  5. Sherman, K. E., et al. (1998). Combination therapy with thymosin alpha1 and interferon for the treatment of chronic hepatitis C infection: a randomized, placebo-controlled double-blind trial. Hepatology, 27(4), 1128-35. PMID: 9537454
  6. Yu, Y., et al. (2009). [Evaluation of efficacy of thymosin alpha1 in the treatment of sepsis: a systematic review]. Zhongguo Wei Zhong Bing Ji Jiu Yi Xue, 21(1), 21-4. PMID: 19141185
  7. Wu, J., et al. (2025). The efficacy and safety of thymosin α1 for sepsis (TESTS): multicentre, double blinded, randomised, placebo controlled, phase 3 trial. BMJ, 388, e082583. PMID: 39814420
  8. Soeroto, A. Y., et al. (2023). The efficacy of thymosin alpha-1 therapy in moderate to critical COVID-19 patients: a systematic review, meta-analysis, and meta-regression. Inflammopharmacology, 31(6), 3317-3325. PMID: 37845598
  9. Wang, Z., et al. (2021). Thymosin Alpha-1 Has no Beneficial Effect on Restoring CD4+ and CD8+ T Lymphocyte Counts in COVID-19 Patients. Front Immunol, 12, 568789. PMID: 34149679
  10. Shehadeh, F., et al. (2023). 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, 227(2), 226-235. PMID: 36056913
  11. Carraro, G., et al. (2012). Thymosin-alpha 1 (Zadaxin) enhances the immunogenicity of an adjuvated pandemic H1N1v influenza vaccine (Focetria) in hemodialyzed patients: a pilot study. Vaccine, 30(6), 1170-80. PMID: 22178096
  12. Chen, C., et al. (2024). Role of thymosin α1 in restoring immune response in immunological nonresponders living with HIV. BMC Infect Dis, 24(1), 97. PMID: 38233816
  13. Lopez, M., et al. (1994). Biochemotherapy with thymosin alpha 1, interleukin-2 and dacarbazine in patients with metastatic melanoma: clinical and immunological effects. Ann Oncol, 5(8), 741-6. PMID: 7826907
  14. Xu, H., et al. (2026). Neoadjuvant immunochemotherapy plus thymalfasin in locally advanced gastric cancer: a prospective clinical trial. BMC Med, 24(1). PMID: 41749205
  15. U.S. Food and Drug Administration. FDA Briefing Document, Pharmacy Compounding Advisory Committee meeting, December 4, 2024 (thymosin alpha-1-related bulk drug substances; nomination withdrawn, FDA proceeding). Read October 3, 2026. FDA
  16. U.S. Food and Drug Administration. Final Summary Minutes of the Pharmacy Compounding Advisory Committee meeting, December 4, 2024 (thymosin alpha-1 vote: 4 yes, 17 no). Read October 3, 2026. FDA
  17. U.S. Food and Drug Administration. Certain Bulk Drug Substances for Use in Compounding that May Present Significant Safety Risks (thymosin-alpha 1 entry). Content current as of April 22, 2026; read October 1, 2026. FDA
  18. U.S. Food and Drug Administration. Pharmacy Compounding Advisory Committee meeting, December 4, 2024: Thymosin alpha-1 (Ta1) related bulk drug substances, FDA presentation. Read October 3, 2026. FDA
  19. Federal Advisory Committee Act database. Pharmacy Compounding Advisory Committee, current fiscal year report (December 4, 2024 votes; agency reviewing recommendations). Read October 3, 2026.
  20. Cheng, Y., et al. (2022). Identification and determination of structurally related peptide impurities in thymalfasin by liquid chromatography-high-resolution mass spectrometry. Anal Bioanal Chem, 414(28), 8035-8045. PMID: 36207535

Educational information, not medical advice. Each dose in this guide names its source, an approved label or a published study. None is a recommendation for you. An unapproved compound has no established safe or effective human dose, and products sold for “research use only” are not made or tested for people. Talk to a doctor before acting on anything on this site, including before you start, stop or change any medicine or dose.

All articles

New guides and rule changes, by email

One short email when a peptide's legal status moves — an FDA or PCAC decision, a WADA list change, an enforcement action — plus new guides and tools. At most one a week, and none when nothing changes. The newsletter has not started sending yet: your first email will be its first issue.

We keep your email address and the page you signed up from, nothing else. How it works · Privacy · RSS instead