Thymosin alpha-1

Origin and structure

Thymosin alpha-1 (Tα1) was first isolated from thymosin fraction 5, an extract of calf thymus that researchers studied for its effects on the immune system. It is a short, strongly acidic peptide of 28 amino acids with an acetyl group on the first one. The medicine is not extracted from animals: thymalfasin, its international non-proprietary name, is made by chemical synthesis and has the same structure as the natural peptide.

SciClone Pharmaceuticals sells thymalfasin as Zadaxin. In Italy it comes as a vial of 1.6 mg of freeze-dried powder with 1 ml of solvent, for injection under the skin or into a muscle. The body clears it quickly: the investigators of the TESTS trial give a half-life of about 1.5 hours, and the Italian product information says blood levels are back to baseline within 24 hours of an injection.

Despite the name, it is unrelated to thymosin beta-4, the protein behind TB-500 (see below).

How it is thought to work

Thymosin alpha-1 is described as an immune modulator rather than a drug with one known target. Laboratory and animal studies report that it activates dendritic cells, the cells that show pathogens to T cells, steers T-helper cells towards the type 1 response that fights infections, and reduces T-cell exhaustion, the worn-out state T cells can reach in sepsis and long-lasting infections. The Italian product information calls it a thymic hormone that acts as an immunomodulator.

The clinical idea is to restore a weakened immune response: in chronic hepatitis B, where the body fails to clear the virus; in sepsis, where the immune system can become exhausted after the first wave of inflammation; in cancer; and in people who respond poorly to vaccines. Effects in the laboratory do not guarantee benefit at the bedside: in TESTS, HLA-DR on monocytes, a marker of how well the immune system is working, ended up no different on thymalfasin than on placebo.

Is thymosin alpha-1 approved?

Yes, as thymalfasin in a number of countries, but not by the EMA or the FDA.

Research-grade thymosin alpha-1, the freeze-dried peptide sold for laboratory use, is not Zadaxin. It has no marketing authorisation anywhere, is not made under a medicines licence, and may not be used in people. The approvals below describe the medicine, not the research peptide.

• EU: no EU-wide marketing authorisation. Italy first authorised Zadaxin on 27 April 1993. There it is indicated as an adjuvant to influenza vaccination in people with weakened immunity, is prescription-only and is not reimbursed (class C, paid in full by the patient). In July 2002 the European Commission granted thymalfasin an orphan designation for hepatocellular carcinoma (liver cancer); a designation is not an approval.
• Netherlands: the CBG's medicines register (Geneesmiddeleninformatiebank) contains no product with thymalfasin, so there is no Dutch medicine to prescribe.
• China and elsewhere: approved in China since 1996 and, according to the manufacturer, also in South Korea, Thailand, Singapore, Indonesia, Cambodia and Argentina, mainly for chronic hepatitis B and as an immune enhancer; some countries also list hepatitis C or immune support during chemotherapy.
• US: never approved. The FDA granted SciClone four orphan designations, for chronic active hepatitis B (1991), DiGeorge anomaly with immune defects (1998), hepatocellular carcinoma (2000) and stage IIb to IV melanoma (2006); none led to an approval. In December 2024 the FDA proposed not to add thymosin alpha-1 to the list of bulk substances that US pharmacies may compound with, and its Pharmacy Compounding Advisory Committee agreed by 17 votes to 4.

What the research shows

Thymosin alpha-1 has been tested in people for decades, mostly in Asia and often in small or open-label trials; the largest recent trial was partly funded by the manufacturer. The main results:

• Chronic hepatitis B (Hepatology 1998): 98 patients were randomised to 26 or 52 weeks of 1.6 mg twice weekly, or to no treatment. Eighteen months after the start, 40.6% of the 26-week group had lost hepatitis B virus DNA and e-antigen, against 26.5% of the 52-week group and 9.4% of the untreated group; only the 26-week difference was statistically significant. Responses kept building up after treatment stopped, and no responder lost the surface antigen.
• Chronic hepatitis B, US phase 3 (J Viral Hepat 1999): 97 patients received 1.6 mg or placebo twice weekly for six months, double-blind. A complete response occurred in 14% against 4% on placebo (P = 0.084), not statistically significant; the authors wrote that the results did not confirm earlier reports.
• Sepsis, earlier trials: a meta-analysis of 10 small randomised trials with 530 patients suggested lower 28-day mortality (22% against 38%), but the quality of that evidence was low.
• Sepsis, TESTS (BMJ 2025): 1,106 adults in 22 Chinese hospitals received 1.6 mg or placebo every 12 hours for up to seven days, double-blind. Among the 1,089 analysed, 28-day mortality was 23.4% against 24.1% (hazard ratio 0.99, 95% CI 0.77 to 1.27). In subgroups, results looked worse in people under 60 (hazard ratio 1.67) and possibly better in people with diabetes (0.58); such subgroup findings need confirmation.
• COVID-19: thymalfasin was commonly given to patients in China in early 2020. In a retrospective study of 771 critically ill patients from 19 hospitals, crude 28-day mortality was lower with it (41.3% against 60.6%), but after matching patients on their condition at baseline it was 51.0% against 52.9%, no difference.
• Metastatic melanoma (J Clin Oncol 2010): 488 patients received dacarbazine with interferon alfa, the same plus thymalfasin at 1.6, 3.2 or 6.4 mg, or dacarbazine with 3.2 mg thymalfasin. Two thymalfasin arms had more tumour responses (10 and 12, against 4 in the control arm); median overall survival was 9.4 months across the thymalfasin arms against 6.6 months, a difference that was not statistically significant (hazard ratio 0.80, P = 0.08).

Thymosin alpha-1 and TB-500: different peptides

The shared name causes confusion. Thymosin alpha-1 and thymosin beta-4 were both found in extracts of the thymus and both carry the name thymosin, but they are unrelated peptides with different sequences and functions. Thymosin beta-4 is a larger protein that binds actin, part of the cell skeleton, and is studied for tissue repair; TB-500 is the name used for it or for a short fragment of it.

The difference matters in sport. Thymosin beta-4 and its derivatives, such as TB-500, are named under S2 of the WADA Prohibited List. Thymosin alpha-1 is not named on the 2026 list or on the 2027 list. The S0 class for non-approved substances covers only substances without current approval by any government health authority, and thymalfasin is authorised in Italy and China.

Side effects and warnings

Few side effects have been reported. The Italian product information lists only occasional mild, short-lived pain at the injection site. In the hepatitis B trial of 98 patients no significant side effects were seen, and in TESTS adverse events (66.4% against 67.6% on placebo) and serious adverse events (26.8% against 29.3%) were as frequent as on placebo.

The Italian label rules it out in pregnancy, during breastfeeding, in children and in people hypersensitive to it. It advises caution in people with atopy or earlier allergic reactions, says use in autoimmune disease should be judged case by case, and asks for caution when it is combined with other immune-modulating medicines. In long-term animal studies, a very high dose (1,000 micrograms per kilogram a day) caused neutropenia, a mild fall in platelets and leucocytosis.

These data describe the licensed medicine. A research peptide has no safety record of its own; its identity and purity are what its certificate of analysis says, nothing more.

Frequently asked questions

Is thymosin alpha-1 the same as TB-500 or thymosin beta-4?

No. Both were found in thymus extracts and share the name thymosin, but they are unrelated peptides. Thymosin alpha-1 has 28 amino acids and is studied as an immune modulator; thymosin beta-4, sold as TB-500, is a larger actin-binding protein studied for tissue repair. Of the two, only thymosin beta-4 and its derivatives are on the WADA Prohibited List.

Is thymosin alpha-1 legal in the Netherlands?

No medicine with thymalfasin is registered in the Netherlands: the CBG's Geneesmiddeleninformatiebank lists none, so there is no Dutch product to prescribe. Within the EU, Zadaxin is authorised in Italy, on prescription, as an add-on to flu vaccination. Research-grade thymosin alpha-1 is not a medicine and may not be used in people.

Is thymosin alpha-1 banned in sport?

It is not named on the WADA Prohibited List for 2026 or 2027. The catch-all class S0 covers substances with no current approval by any government health authority, and thymalfasin is authorised in Italy and China. Thymosin beta-4 and TB-500 are a different matter: they are prohibited at all times under S2.

Is thymosin alpha-1 FDA-approved?

No. It has four FDA orphan designations, granted between 1991 and 2006, but an orphan designation is not an approval and none of them led to one. In December 2024 the FDA proposed not to allow it as a bulk substance for pharmacy compounding, and its advisory committee agreed by 17 votes to 4.

Does thymosin alpha-1 help in sepsis or COVID-19?

Not on current evidence. Small early sepsis trials looked promising, but TESTS, a double-blind trial of 1,106 patients, found 28-day mortality of 23.4% with thymalfasin against 24.1% with placebo. For COVID-19 the data come mainly from Chinese hospital records; in the largest such study, of 771 critically ill patients, mortality did not differ once patients were matched on their condition.

Does thymosin alpha-1 boost the immune system of healthy people?

That has not been shown. The human trials enrolled patients: people with chronic hepatitis B, sepsis, cancer or COVID-19, or people who respond poorly to vaccination. Even in those groups the results are mixed, and the approved uses are narrow: hepatitis B in China and other countries, and support for flu vaccination in Italy.

Storage and handling

Store according to product-label instructions and batch handling notes. Lyophilized research peptides are commonly kept dry, protected from light, and handled with clean laboratory technique.

References

Checked against these sources on 28 October 2026.

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