Does thymosin alpha-1 boost the immune system and prevent infections?

What it is and where it is approved

Thymosin alpha-1 is a peptide that helps activate and regulate several types of immune cells. Its synthetic form is known as thymalfasin and sold as Zadaxin. A 2015 review noted that it has been used in thousands of patients and tested in hepatitis B and C, sepsis and other infections, but that basic questions about dosing and the right trial endpoints had not been settled.

SciClone Pharmaceuticals licensed the drug in the early 1990s for regions of the world outside the United States and Europe and, by 2007, reported approvals in more than 30 countries. In the US, the FDA lists thymosin alpha-1 among bulk drug substances that may present significant safety risks in compounding, citing a possible risk of immune reactions, impurities and inadequate safety information.

Sources: PubMed 26098768 · PubMed 17947591 · PubMed 22178096 · PubMed 36056913 · fda.gov

Hepatitis B and C

For chronic hepatitis B, a 2026 Cochrane review found 10 randomized trials with 1,349 participants. Thymosin alpha-1 may reduce deaths and serious adverse events, but the certainty of the evidence was rated very low or low because of bias, small numbers and inconsistent results. The reviewers concluded that they could not be sure whether it helps.

In hepatitis C, a European trial in 552 patients who had not responded to earlier treatment added thymosin alpha-1 or placebo to standard interferon-based therapy. Overall cure rates were similar in both groups. The authors concluded that the drug seems to play no role in primary treatment, and suggested only that it might help prevent relapse in some patients, an idea that would need its own trial.

Sources: PubMed 42713852 · PubMed 22233415

Sepsis: an early signal that a large trial did not confirm

The 2013 ETASS trial in 361 patients with severe sepsis in China reported 28-day death rates of 26.0% with thymosin alpha-1 and 35.0% in the control group, a borderline result. The trial was single-blind rather than double-blind, which leaves more room for bias. An immune marker on monocytes (HLA-DR) also improved more in the treated group.

The much larger TESTS trial was designed to settle the question. It enrolled 1,106 adults with sepsis at 22 Chinese hospitals and was double-blind and placebo-controlled. Death at 28 days was 23.4% with thymosin alpha-1 and 24.1% with placebo, with no difference in any secondary or safety outcome. The trial was partly supported by SciClone. A 2025 meta-analysis found an overall mortality benefit across 11 trials, but not when it was limited to high-quality or multicenter trials, and it judged the total sample size inadequate.

Sources: PubMed 23327199 · PubMed 39814420 · PubMed 40969554

Does it prevent infections?

The most direct test of infection prevention is the TRACE trial, published in 2022. It randomized 508 patients with severe acute necrotizing pancreatitis, a condition in which dead pancreatic tissue often becomes infected, to thymosin alpha-1 or placebo. Infected pancreatic necrosis developed in 15.7% of the treated group and 18.1% of the placebo group, a difference that was not statistically significant. Other complications did not differ either.

Evidence for better vaccine responses is more positive but small. In a pilot study of about 100 hemodialysis patients given a pandemic H1N1 flu vaccine, those who also received thymosin alpha-1 had higher antibody levels at day 21, although levels fell faster by day 42. A 2007 summary by NIH researchers reported that trials in older adults showed enhanced flu vaccine responses. Higher antibody levels are a reasonable sign, but these studies were not large enough to show fewer actual infections.

Sources: PubMed 35713670 · PubMed 22178096 · PubMed 17600281

COVID-19

Thymosin alpha-1 was widely used in China early in the pandemic. A 2020 retrospective study of 76 patients with severe COVID-19 in Wuhan reported lower mortality in treated patients and recovery of T-cell counts. But a larger retrospective study of 771 critically ill patients in 19 hospitals found that, after matching treated and untreated patients on their baseline characteristics, 28-day mortality was 51.0% versus 52.9%, with no meaningful difference.

A 2023 meta-analysis of nine studies covering more than 5,000 patients found no significant effect on mortality and concluded that the results do not support its use in hospitalized adults with COVID-19. A small randomized, open-label pilot trial in the US found that CD4 T-cell counts rose faster with thymosin alpha-1, but clinical recovery was not significantly different from standard care.

Sources: PubMed 32442287 · PubMed 33208294 · PubMed 36527881 · PubMed 36056913

Boosting markers versus preventing illness

Across these studies, thymosin alpha-1 often moves immune measurements in the expected direction, including the monocyte marker HLA-DR in sepsis and T-cell counts in COVID-19. That gives some support to the idea that it "boosts" parts of the immune system.

But changes in immune markers have not reliably translated into fewer infections or deaths when tested in large, double-blind trials. For healthy people, no trial we found tested whether thymosin alpha-1 prevents everyday infections. The claim holds up for immune markers and possibly vaccine responses in specific groups, but not as a general infection-prevention tool.

Sources: PubMed 23327199 · PubMed 36056913 · PubMed 39814420 · PubMed 35713670

Profiles

Thymosin alpha-1 profile →

References

1. Historical review of thymosin α 1 in infectious diseases. Expert Opin Biol Ther · 2015 · PMID 26098768
2. Issues in pharmaceutical development of thymosin alpha1 from preclinical studies through marketing. Ann N Y Acad Sci · 2007 · PMID 17947591
3. Thymosin-alpha 1 (Zadaxin) enhances the immunogenicity of an adjuvated pandemic H1N1v influenza vaccine (Focetria) in hemodialyzed patients: a pilot study. Vaccine · 2012 · PMID 22178096
4. 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 · PMID 36056913
5. Thymosin-ɑ1 for people with chronic hepatitis B. Cochrane Database Syst Rev · 2026 · PMID 42713852
6. Thymosin alpha-1 with peginterferon alfa-2a/ribavirin for chronic hepatitis C not responsive to IFN/ribavirin: an adjuvant role? J Viral Hepat · 2012 · PMID 22233415
7. The efficacy of thymosin alpha 1 for severe sepsis (ETASS): a multicenter, single-blind, randomized and controlled trial. Crit Care · 2013 · PMID 23327199
8. The efficacy and safety of thymosin α1 for sepsis (TESTS): multicentre, double blinded, randomised, placebo controlled, phase 3 trial. BMJ · 2025 · PMID 39814420
9. Efficacy of thymosin α1 for sepsis: a systematic review and meta-analysis of randomized controlled trials. Front Cell Infect Microbiol · 2025 · PMID 40969554
10. Immune enhancement in patients with predicted severe acute necrotising pancreatitis: a multicentre double-blind randomised controlled trial. Intensive Care Med · 2022 · PMID 35713670
11. Thymosin alpha 1 as an adjunct to influenza vaccination in the elderly: rationale and trial summaries. Ann N Y Acad Sci · 2007 · PMID 17600281
12. 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 · PMID 32442287
13. The effect of thymosin α1 on mortality of critical COVID-19 patients: A multicenter retrospective study. Int Immunopharmacol · 2021 · PMID 33208294
14. Thymosin alpha1 use in adult COVID-19 patients: A systematic review and meta-analysis on clinical outcomes. Int Immunopharmacol · 2023 · PMID 36527881

Other sources

• https://www.fda.gov/drugs/human-drug-compounding/certain-bulk-drug-substances-use-compounding-may-present-significant-safety-risks

These are original summaries of published research, written with AI assistance and checked against the cited sources. They are not medical advice and have not been reviewed by a clinician. Every PubMed reference was checked against PubMed's record for title, year and journal. All claim checks · Editorial standards