Thymosin alpha-1: what 30 trials and a failed sepsis study actually showed

Thymosin alpha-1 has been studied in more than 11,000 people across about 30 controlled trials. In January 2025, the largest trial yet found it did nothing for sepsis. Read together with the other 2025 results, that null result says a lot about what this peptide has and has not been shown to do.

This page summarises the human record. It is not a recommendation: thymosin alpha-1 is not approved by the FDA for any use, and decisions about any treatment belong to you and a licensed clinician.

What thymosin alpha-1 is and how it acts

Thymosin alpha-1 is a 28-amino-acid peptide made by the thymus gland. Thymic output declines with age. In laboratory studies, the peptide binds Toll-like receptors 2 and 9 on dendritic cells and T cells and shifts immune activity toward the Th1 arm, the part of the immune system involved in fighting viruses and abnormal cells.

In a 2021 study in Open Forum Infectious Diseases, researchers gave thymosin alpha-1 to 15 patients with COVID-19 and measured immune markers in their blood. Treatment reduced CD38 expression on CD8+ T cells (P=0.044), lowered intracellular IL-6 in those cells (P=0.050) and reduced HLA-DR activation (P=0.001). It was a small, uncontrolled study of blood markers, not of clinical outcomes.

"CD38 expression in CD8+ T cells correlated positively with blood IFNgamma mRNA levels (rho=0.589, P=.021): the first direct link between thymosin alpha-1, CD38, and interferon signaling in humans."

Open Forum Infectious Diseases, 2021

Why the largest sepsis trial found no benefit

The TESTS trial, published in the BMJ in January 2025, enrolled 1,089 patients with sepsis across multiple centres in China, randomised them to thymosin alpha-1 or placebo, and measured 28-day mortality. Mortality was 23.4% on thymosin alpha-1 and 24.1% on placebo: hazard ratio 0.99, P=0.93. There was no difference.

Earlier, smaller and mostly single-centre trials had reported positive results in sepsis. The TESTS investigators pointed to the design of those earlier studies as the likely reason. It is a familiar pattern: promising small trials, then a large, well-designed one that finds no effect.

Severe acute pancreatitis: the strongest recent result

A 2025 meta-analysis in Frontiers in Immunology pooled five randomised controlled trials covering 706 patients with severe acute pancreatitis, a condition in which the immune response to pancreatic damage can become dysregulated.

In the pooled trials, thymosin alpha-1 was associated with higher CD4+ counts, an improved CD4+/CD8+ ratio, 40% fewer bloodstream infections and 62% fewer abdominal infections. APACHE II severity scores fell more in the thymosin alpha-1 groups. These were hospital trials in a serious acute illness, run by clinicians.

Long COVID: a hypothesis, not a result

Long COVID and ME/CFS have been linked in research to persistent T-cell activation alongside immune exhaustion. A 2023 study reported that thymosin alpha-1 changed the CD38 and interferon-gamma activation pattern in patients after SARS-CoV-2 infection. No randomised trial of thymosin alpha-1 for long COVID or ME/CFS has been published, so whether it helps either condition is unknown.

What the hepatitis B trials found

The most rigorous long-term data come from chronic hepatitis B, the main approved use of Zadaxin outside the US. In those trials, participants with chronic hepatitis B were treated for 26 weeks. The trials reported a complete virological response rate of about 40.6%, with the peak response measured at week 52, six months after treatment ended.

That delayed response is one of the more distinctive findings in the thymosin alpha-1 literature. It comes from a specific infection, in trials supervised by hepatologists, and it does not tell us what would happen in any other setting.

Across the trial record, no treatment-limiting toxicity has been reported. The most common side effect was mild local skin reactions in roughly 5 to 8% of participants; transient fatigue and muscle aches were reported rarely. Immune-modulating drugs carry a recognised rejection concern in organ transplant recipients.

Regulatory status in 2026

Thymosin alpha-1 is not approved by the FDA for any indication. It holds orphan drug designation for several conditions, which is a research status rather than an approval. Its status on FDA's compounding lists has changed more than once since 2024 and has been under review during 2026; check FDA's current position rather than relying on any website, this one included.

Outside the US, it is approved as Zadaxin (SciClone Pharmaceuticals) in more than 35 countries, including China, Italy, the Philippines, India and South Korea, mainly for chronic hepatitis B.

What genetics can and cannot tell you

No pharmacogenomic study of thymosin alpha-1 has been published. Genes involved in immune activation, such as HLA class II genes, IL6 and IFNG, carry common variants associated with differences in inflammation and immune response, and the COVID-19 blood study above measured some of the same markers. That overlap is a reason researchers might study these genes alongside thymosin alpha-1 in future. It is not evidence that any genotype changes response.

Thymosin alpha-1 is a peptide broken down by peptidases, not by the liver CYP enzymes, so CYP genotypes are not relevant to how it is cleared. See the thymosin alpha-1 reference page for the full evidence summary.