Thymosin alpha-1 (Tα1) is a 28-amino-acid peptide first isolated from calf thymus in 1977. Its synthetic version, thymalfasin, is sold under the brand name Zadaxin in a number of countries outside the US, mainly for chronic hepatitis B and as an add-on to influenza vaccination in people with weak immune systems. In the US it is sold online and by some compounders, marketed for conditions ranging from hepatitis and COVID-19 to Lyme disease and chronic fatigue (FDA briefing document, 2024).
The single most important fact: thymosin alpha-1 is not FDA-approved, and the largest placebo-controlled trial ever run, in 1,106 adults with sepsis, found no effect on survival. In 2024 FDA reviewers concluded that there is a lack of evidence for its effectiveness in any of the 12 uses they examined, and an FDA advisory committee voted 17–4 against allowing pharmacies to compound it. We found no human study testing it for muscle growth, recovery or athletic performance.
This page summarizes what FDA’s review, foreign product labels and the clinical trials report. It is for education only and is not medical advice.
| Property | Detail |
|---|---|
| Class | Natural thymic peptide; immunomodulator (immune-system modifier) |
| Other names | Thymalfasin (synthetic form), Zadaxin (brand), Tα1, Ta1 |
| Structure | 28 amino acids, acetylated at the starting end; C₁₂₉H₂₁₅N₃₃O₅₅, 3,108.3 g/mol (FDA) |
| Route and studied dose | Subcutaneous injection; 1.6 mg twice weekly in most hepatitis trials; 1.6 mg every 12 h for 7 days in the largest sepsis trial |
| Half-life (humans) | About 2 h after subcutaneous injection (means 1.8–2.6 h in healthy volunteers) |
| Approval | Not FDA-approved; licensed in several other countries, e.g. Italy (flu-vaccine adjuvant), India and Indonesia (chronic hepatitis B) |
| US compounding | Not on the 503A bulks list; FDA advisory committee voted 17–4 against adding it (2024); on FDA’s list of substances that may present significant safety risks (2026) |
| WADA | Not named on the 2026 Prohibited List |
What it is
Origin and structure
Allan Goldstein’s group purified thymosin alpha-1 from “thymosin fraction 5,” a calf thymus extract, and sequenced it in 1977. They described it as a heat-stable, highly acidic peptide of 28 amino acids (Goldstein et al., PNAS 1977). In 1984 researchers found that the thymus does not actually store Tα1 as such. It holds a larger protein of about 112 amino acids, prothymosin alpha, whose first 28 amino acids are the Tα1 sequence. Tα1 appears to be cut from it during the extraction process (Haritos et al., PNAS 1984).
The drug form, thymalfasin, is made by solid-phase chemical synthesis and has the same sequence as the natural peptide. FDA lists its formula as C₁₂₉H₂₁₅N₃₃O₅₅ and its molecular weight as 3,108.3 g/mol. Because it contains many aspartic and glutamic acid residues, it is strongly acidic, with an isoelectric point of 4.2 (FDA briefing document, 2024). Healthy adults have low natural blood levels, about 0.1–1 ng/mL.
Not the same as other “thymus peptides”
Several unrelated peptides are sold under similar names. They differ in size, structure and evidence, and results for one cannot be applied to another:
| Peptide | What it is | Library page |
|---|---|---|
| Thymosin alpha-1 (thymalfasin) | 28 amino acids; immunomodulator; licensed abroad as Zadaxin | This page |
| Thymosin beta-4 / TB-500 | Thymosin beta-4 is a 43-amino-acid peptide also purified from thymosin fraction 5 (Low et al., PNAS 1981). TB-500 is a short synthetic fragment of it | TB-500 (Thymosin Beta-4) |
| Thymulin | A thymic hormone (serum thymic factor) that is only active when bound to zinc (Dardenne et al., PNAS 1982) | Thymulin |
| Thymalin | A mixture of natural peptides extracted from calf thymus, developed in Russia (Morozov & Khavinson 1997) | Thymalin |
| Thymagen (Thymogen) | A synthetic dipeptide (glutamic acid–tryptophan) originally isolated from thymalin (Morozov & Khavinson 1997) | Thymagen |
Despite the shared “thymosin” name, thymosin alpha-1 (28 amino acids) and thymosin beta-4 (43 amino acids) are different molecules. The name only reflects that both were first purified from the same calf thymus extract.
Proposed mechanism
Most mechanism data come from cell culture and mice. FDA’s review summarized the reported effects as follows (FDA briefing document, 2024):
- more activity of natural killer (NK) cells, which kill infected and tumor cells;
- a shift of helper T cells toward the Th1 type, with more interleukin-2 and interferon-gamma;
- more cytotoxic CD8+ T cells;
- activation of dendritic cells, the cells that present antigens to start an immune response.
In mouse studies, Tα1 activated dendritic cells through Toll-like receptor signaling, the receptor family that detects bacteria, fungi and viruses (Romani et al., Blood 2004). FDA cautioned that most animal studies used doses far above human doses. One in-vitro anti-HIV effect needed concentrations about 2,000 times higher than the peak blood levels reached with the usual 1.6 mg dose.
Pharmacokinetics
The key human study gave 900 µg/m² of body surface area (actual doses 1.6–2.2 mg) under the skin to nine healthy volunteers. It compared three products, including Zadaxin, in a crossover design with single doses and 5 days of daily dosing (Rost et al., Int J Clin Pharmacol Ther 1999):
| Measure | Result |
|---|---|
| Time to peak | 1–2 h |
| Peak concentration | 30–80 µg/L (ng/mL), vs natural levels mostly under 0.1 µg/L |
| Elimination half-life | Under 3 h (product means 1.8–2.6 h) |
| Volume of distribution | 30–40 L, consistent with spread through the fluid outside cells |
| Accumulation with daily dosing | None seen over 5 days |
| Effect of product | Exposure was higher with one of the three products (Timosina) |
FDA summarized the human data as a time to peak of about 2 hours and a serum half-life of about 2 hours (FDA briefing document, 2024). Blood levels are back near baseline within a day. Most trials nonetheless dosed only twice a week, so for most of each dosing interval little or no drug remains in the blood.
Regulatory status
Outside the US
FDA’s review, citing foreign drug databases, lists approvals for Zadaxin or thymalfasin in, among others (FDA briefing document, 2024):
- Italy: 1.6 mg injection as an adjuvant to influenza vaccination in immunocompromised people, twice weekly for 4 weeks after each vaccine dose;
- India and Indonesia: chronic hepatitis B in adults with compensated liver disease and active viral replication; the Indonesian label gives 1.6 mg twice weekly for 6 months;
- Hong Kong: approved product listed;
- Singapore and Mexico: product monographs list chronic hepatitis B, plus hepatitis C in Singapore and flu-vaccine adjuvant use in Mexico.
The manufacturer’s reports describe further approvals in Asia, Latin America, Eastern Europe and the Middle East, which FDA said it could not independently verify. Tα1 is not in the European or Japanese Pharmacopoeia. The EMA granted it orphan designation for hepatocellular carcinoma (liver cancer), which supports development but is not a marketing approval.
United States
Thymosin alpha-1 is not part of any FDA-approved drug. It holds four US orphan drug designations, which also are not approvals (FDA briefing document, 2024).
- Compounding review, 2024. FDA evaluated thymosin alpha-1 and its acetate salt for the list of bulk substances that pharmacies may compound under section 503A. Reviewers found the substances poorly characterized and raised concerns about immunogenicity (the risk of the body forming antibodies against the peptide). They concluded there was a lack of evidence of effectiveness for hepatitis B, hepatitis C, HIV, COVID-19, vaccine response, melanoma, liver cancer, lung cancer, sepsis, infections after stem cell transplant, COPD and chronic fatigue syndrome.
- Advisory committee vote. On December 4, 2024, the Pharmacy Compounding Advisory Committee voted 17–4 against adding the free base and 17–4 against adding the acetate. Several members who voted no said there was no compelling evidence of effectiveness and safety (FDA meeting minutes).
- Safety-risk list. As of its April 22, 2026 update, FDA’s list of bulk substances that may present significant safety risks includes thymosin alpha-1, citing immunogenicity, peptide impurities and inadequate safety information (FDA).
Sport
Thymosin alpha-1 is not named on the 2026 WADA Prohibited List, which does name thymosin beta-4 and TB-500 (WADA 2026 Prohibited List). The list’s S0 class bans substances “with no current approval by any governmental regulatory health authority,” and thymalfasin holds approvals in several countries. We found no specific WADA ruling on it.
What the research shows
Most trials were small, open-label or run before current standard treatments existed. Many were funded by the manufacturer. The table summarizes the strongest data by use:
| Use | Best evidence | Bottom line |
|---|---|---|
| Sepsis | Double-blind phase 3 RCT, n = 1,106 | No effect on 28-day mortality |
| Chronic hepatitis B | Cochrane review, 10 RCTs, n = 1,349 | Very low-certainty evidence; benefit uncertain |
| Chronic hepatitis C | Placebo-controlled RCT with old interferon therapy, n = 109 | Higher response rates than interferon alone; obsolete since modern antivirals |
| COVID-19 | Meta-analysis of 9 studies, n = 5,352 | No mortality effect overall |
| Metastatic melanoma | Randomized phase 2, n = 488 | Some extra responses; survival difference not significant |
| Muscle, recovery, performance | None | Not studied in humans |
Sepsis
Sepsis is the setting with the best trials. The first multicenter trial, ETASS, randomized 361 patients with severe sepsis in China to Tα1 (1.6 mg twice daily for 5 days, then once daily for 2 days) or control, with only patients blinded (Wu et al., Crit Care 2013). Mortality at 28 days was 26.0% with Tα1 and 35.0% with control (RR 0.74, 95% CI 0.54–1.02), a borderline result.
The follow-up phase 3 trial, TESTS, was designed to confirm it. It randomized 1,106 adults with sepsis at 22 Chinese centers to 1.6 mg Tα1 or placebo under the skin every 12 hours for 7 days, with patients and doctors blinded (Wu et al., BMJ 2025):
| Outcome | Thymosin alpha-1 (n = 542) | Placebo (n = 547) |
|---|---|---|
| 28-day all-cause mortality | 23.4% | 24.1% |
| Hazard ratio | 0.99 (95% CI 0.77–1.27) | — |
| Any adverse event | 66.4% | 67.6% |
| Serious adverse event | 26.8% | 29.3% |
No secondary outcome differed. A prespecified subgroup analysis hinted at possible benefit in patients 60 or older and possible harm in those under 60 (HR 1.67, 95% CI 1.04–2.67), but subgroup findings like these are hypothesis-generating only. The trial was partly funded by SciClone, Zadaxin’s maker.
A 2025 meta-analysis of 11 RCTs (1,927 patients) found lower mortality overall (OR 0.73, 95% CI 0.59–0.90). The benefit disappeared when only high-quality trials (OR 0.82, 95% CI 0.65–1.03) or multicenter trials (OR 0.86, 95% CI 0.68–1.08) were analyzed (Gu et al., Front Cell Infect Microbiol 2025). FDA noted that all sepsis trials were conducted in China and that sepsis guidelines do not mention Tα1.
Chronic hepatitis B
This is one of Tα1’s main licensed uses abroad, but the evidence is weak. In a US phase 3 trial, 97 patients received 1.6 mg Tα1 or placebo twice weekly for 6 months (Mutchnick et al., J Viral Hepat 1999). A complete response (sustained loss of viral DNA and the HBeAg marker) occurred in 14% vs 4% (P = 0.084). The authors wrote that the results did not confirm earlier reports of efficacy.
A 2026 Cochrane review pooled 10 RCTs with 1,349 adults, published between 1991 and 2018 (Naing et al., Cochrane 2026):
| Outcome | Risk ratio (95% CI) | Trials, patients | Certainty |
|---|---|---|---|
| All-cause mortality | 0.53 (0.29–0.96) | 3, 907 | Very low |
| Serious adverse events | 0.72 (0.53–0.99) | 5, 1,056 | Low |
| Hepatitis B-related illness | 0.86 (0.54–1.40) | 3, 854 | Very low |
The reviewers concluded they were “not sure” whether Tα1 reduces mortality or serious adverse events, because of risk of bias and imprecision. FDA added that many trials used outdated comparators such as interferon, and that there is no evidence Tα1 adds benefit to current standard treatment (FDA briefing document, 2024).
Chronic hepatitis C
A US double-blind trial randomized 109 patients to Tα1 1.6 mg twice weekly plus interferon, interferon alone, or placebo for 26 weeks (Sherman et al., Hepatology 1998):
| Outcome | Tα1 + interferon | Interferon alone | Placebo |
|---|---|---|---|
| Normal ALT at end of treatment | 37.1% | 16.2% | 2.7% |
| HCV RNA cleared at end of treatment | 37.1% | 18.9% | — |
| Sustained ALT response | 14.2% | 8.1% | — |
These results come from the interferon era. Modern oral antivirals cure most hepatitis C, and FDA found no data on whether adding Tα1 to them helps.
COVID-19
Tα1 has been widely used to treat COVID-19. A meta-analysis of 9 studies with 5,352 patients found no effect on mortality (RR 1.03, 95% CI 0.60–1.75), with very high heterogeneity between studies (I² = 90%), and concluded the data do not support its use in hospitalized adults (Shang et al., Int Immunopharmacol 2023). A small US open-label randomized pilot (n = 49) found no significant difference in clinical recovery, though CD4+ T-cell counts rose faster in one subgroup (Shehadeh et al., J Infect Dis 2023).
Metastatic melanoma
A randomized phase 2 study assigned 488 patients to five arms combining dacarbazine chemotherapy with Tα1 (1.6, 3.2 or 6.4 mg), interferon alfa, or both (Maio et al., J Clin Oncol 2010). The two 3.2 mg Tα1 arms had 10 and 12 tumor responses vs 4 in the control arm. Median overall survival was 9.4 months with Tα1 vs 6.6 months without (HR 0.80, P = 0.08), not statistically significant. Today’s melanoma immunotherapies have replaced the regimens used as the comparator.
Vaccine response and other uses
Small studies in older adults and people with end-stage kidney disease reported higher antibody levels when Tα1 was added to flu vaccines. FDA judged them exploratory, with variable results and no link to clinical outcomes such as influenza illness (FDA briefing document, 2024). FDA reached the same “insufficient evidence” conclusion for HIV, liver cancer, lung cancer, infections after stem cell transplant, COPD and chronic fatigue syndrome.
Muscle, recovery and performance
We found no controlled human study of thymosin alpha-1 for muscle growth, injury recovery, body composition or athletic performance. Claims in these areas extrapolate from its immune effects and have no direct support.
Side effects and risks
Tolerability in trials
Across trials, Tα1 at doses of about 1–16 mg under the skin, for up to 12 months, was generally well tolerated. The most common reactions were local irritation, redness or discomfort at the injection site (FDA briefing document, 2024). In the TESTS sepsis trial, adverse and serious adverse event rates were similar to placebo (see table above). The Indonesian Zadaxin label reports drug-related adverse events in under 1% of more than 2,000 people. Rare events listed there include rash, redness, joint pain with hand swelling and transient muscle atrophy.
Specific signals
FDA’s review highlighted several findings from individual studies:
- Liver enzyme flares in hepatitis B. In a Japanese trial of 316 patients, 22 had transient rises in liver enzymes (ALT), and therapy was paused in 16; all recovered (Iino et al., J Viral Hepat 2005). The Indonesian label also warns of ALT flares.
- Thyroid changes with interferon. Two patients on Tα1 plus interferon had transient TSH suppression followed by elevation (Sherman et al., Hepatology 1998). Interferon alone can cause this, so the role of Tα1 is unclear.
- Stem cell transplant. In one small series, 1 of 6 transplant recipients given Tα1 with donor lymphocytes developed fatal immune hemolytic anemia (destruction of red cells by the immune system). FDA said it is unclear whether Tα1 contributed, but noted a concern about graft-versus-host disease and graft failure in this setting.
Who should not use it, per foreign labels
- Deliberately immunosuppressed patients, such as organ transplant recipients: considered contraindicated unless benefits clearly outweigh risks (Indonesia).
- Children: should not be used (Italy).
- Pregnancy and breastfeeding: contraindicated (Italy).
- People with allergies or atopy: use with caution (Italy).
- Autoimmune disease: evaluate case by case (Italy).
- Other immune-modifying drugs: use caution in combination (Italy).
Immunogenicity and product quality
As a 28-amino-acid peptide injected under the skin, Tα1 may trigger antibodies against itself, a risk FDA said can be amplified by aggregation (peptide molecules clumping together) and manufacturing impurities. FDA found no published data on impurities, aggregates, microbial load or bacterial endotoxins for the bulk substances. It also noted that the 3 mg/mL compounded injection proposed to it is stronger than any product tested in trials (maximum 2 mg/mL), and that compounded Tα1 is also sold as a nasal spray (FDA briefing document, 2024). Product bought as a “research peptide” has no regulatory control over identity, dose or sterility.
Key takeaways
- A real drug abroad, not in the US. Thymalfasin (Zadaxin) is licensed in several countries for hepatitis B and as a flu-vaccine adjuvant, but it has never been FDA-approved.
- The biggest trial was negative. In 1,106 adults with sepsis, Tα1 did not change 28-day mortality (23.4% vs 24.1%). Earlier positive signals came from smaller, less rigorous studies.
- Short-lived in the blood. Peak levels come 1–2 hours after injection and the half-life is about 2 hours, with no build-up on daily dosing.
- Generally well tolerated, with caveats. Injection-site reactions are the main side effect. Liver enzyme flares in hepatitis B and caution with transplant or immunosuppressed patients are documented.
- FDA and its advisers said no to compounding. Reviewers found insufficient evidence for 12 uses, the committee voted 17–4 against, and FDA lists it as a potential safety risk.
- Different from TB-500 and thymulin. Thymosin beta-4/TB-500, thymulin, thymalin and thymagen are separate molecules with separate evidence.
Sources
- Food and Drug Administration. FDA briefing document: Evaluation of thymosin alpha-1 (Ta1)-related bulk drug substances (Ta1 (free base) and Ta1 acetate) for inclusion on the 503A bulk drug substances list. Pharmacy Compounding Advisory Committee meeting, December 4, 2024 (memo dated November 15, 2024). FDA.
- Food and Drug Administration. Summary minutes of the Pharmacy Compounding Advisory Committee meeting, December 4, 2024. FDA.
- Food and Drug Administration. Certain bulk drug substances for use in compounding that may present significant safety risks. Content current as of April 22, 2026. FDA.
- 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. PubMed.
- 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. PubMed.
- 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. PubMed.
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- 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. PubMed.
- 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. PubMed.
- 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. PubMed.
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- World Anti-Doping Agency. The 2026 Prohibited List: International Standard. In effect January 1, 2026. WADA 2026 Prohibited List.