Monograph in Immune & host-defense peptides
Thymosin alpha-1
A 28-residue thymic peptide with dozens of randomized trials, mostly in China and Japan. The largest, a 2025 sepsis trial in the BMJ, found no effect on survival.
Also called Thymalfasin · Tα1 · Ta1 · Zadaxin
Best evidence: Randomized human trials
Randomized controlled trials exist, including a 1,106-patient phase 3 sepsis trial (neutral) and a 316-patient hepatitis B trial; no approved application in Drugs@FDA.
Not FDA-approved · FDA compounding nomination withdrawn
Residue Editorial Team · updated
What is Thymosin alpha-1?
Thymosin alpha-1 (thymalfasin) is a 28-amino-acid thymic peptide studied as an immune modulator1PubMedThe efficacy and safety of thymosin alpha-1 in Japanese patients with chronic hepatitis B; results from a randomized clinical trial. Iino S et al. J Viral Hepat. 2005.,2PubMedThymosin alpha 1: A comprehensive review of the literature. Dominari A et al. World J Virol. 2020.. Its largest trial, TESTS, randomized 1,106 adults with sepsis and found no difference in 28-day mortality (23.4% versus 24.1%)3PubMedThe efficacy and safety of thymosin α1 for sepsis (TESTS): multicentre, double blinded, randomised, placebo controlled, phase 3 trial. Wu J et al. BMJ. 2025.. Hepatitis B trials reported viral and liver-enzyme responses1. It is not FDA-approved, and its compounding nomination was withdrawn4FDACertain Bulk Drug Substances for Use in Compounding that May Present Significant Safety Risks. U.S. FDA, content current as of 04/22/2026..
Key findings
- TESTS (22 Chinese centers, 2016–2020): 28-day all-cause mortality 23.4% with Tα1 versus 24.1% with placebo, hazard ratio 0.99 (0.77 to 1.27); no secondary or safety outcome differed3.
- The earlier single-blind ETASS trial (361 patients with severe sepsis) reported 26.0% versus 35.0% mortality with a marginal P value5PubMedThe efficacy of thymosin alpha 1 for severe sepsis (ETASS): a multicenter, single-blind, randomized and controlled trial. Wu J et al. Crit Care. 2013..
- In 316 Japanese patients with chronic hepatitis B given 0.8 or 1.6 mg for 24 weeks, 36.4% in the 1.6 mg group had normal ALT a year after stopping1.
- A meta-analysis of four RCTs (199 patients) found Tα1 inferior to interferon alpha at end of treatment but superior six months after treatment6PubMedComparison of the efficacy of thymosin alpha-1 and interferon alpha in the treatment of chronic hepatitis B: a meta-analysis. Yang YF et al. Antiviral Res. 2008..
- In a 49-patient open-label COVID-19 trial, clinical recovery was not significantly improved, though CD4+ T-cell counts rose faster7PubMedA Pilot Trial of Thymalfasin (Thymosin-α-1) to Treat Hospitalized Patients With Hypoxemia and Lymphocytopenia Due to Coronavirus Disease 2019 Infection. Shehadeh F et al. J Infect Dis. 2023..
What is Thymosin alpha-1, chemically?
| PubChem CID | 16130571 “Thymalfasin” |
|---|---|
| Formula | C129H215N33O55 |
| Molecular weight | 3,108.3 g/mol |
| CAS (as listed) | 62304-98-7, 69521-94-4, 1337515-90-8 |
| FDA UNII | W0B22ISQ1C |
| InChIKey | NZVYCXVTEHPMHE-ZSUJOUNUSA-N |
| Length | 28 residues |
| Route in trials | Subcutaneous injection (trials) |
| Mechanism | Immune modulator; proposed to enhance and restore T-cell function |
- Hydrophobic
- Polar
- Basic (+)
- Acidic (−)
What is thymosin alpha-1?
Thymosin alpha-1 (Tα1) is a peptide that occurs naturally in the thymus and has long been recognized for modifying, enhancing and restoring immune function2. Thymalfasin, its synthetic form, is a 28-amino-acid polypeptide1,7; PubChem lists the formula C129H215N33O558PubChemPubChem compound record: Thymalfasin. C129H215N33O55 · MW 3108.3 g/mol..
How is thymosin alpha-1 thought to work?
It is classed as an immunomodulatory drug3. Reviews describe uses in immunocompromised states and malignancies, as a vaccine-response enhancer, and in sepsis and infections2. In trials, the measurable effects have been on immune markers: monocyte HLA-DR in sepsis5 and CD4+ T-cell counts in COVID-197.
What have studies found?
Sepsis. ETASS, a single-blind trial in six Chinese hospitals, randomized 361 patients with severe sepsis; 28-day mortality was 26.0% with Tα1 and 35.0% with control (P=0.062 nonstratified; log-rank P=0.049)5. The confirmatory double-blind TESTS trial randomized 1,106 adults at 22 centers and found 23.4% versus 24.1% mortality, concluding there was no clear evidence that Tα1 reduces 28-day mortality3.
Chronic hepatitis B. A Japanese trial randomized 316 patients to 0.8 or 1.6 mg for 24 weeks. A year after stopping, 36.4% of the 1.6 mg group had normal ALT and 22.8% had cleared HBe antigen; adverse reactions were mild1. A meta-analysis of four small RCTs found Tα1 less effective than interferon alpha at the end of treatment but more effective six months later6.
COVID-19. An open-label randomized trial in 49 hospitalized patients with hypoxemia and lymphocytopenia found no significant difference in clinical recovery; CD4+ counts rose faster in treated patients on low-flow oxygen7.
Registered trials. ClinicalTrials.gov lists dozens of studies, many in sepsis, lung cancer and liver disease9TrialClinicalTrials.gov registry search: thymosin alpha 1 OR thymalfasin. 65 registered studies at fetch..
Is Thymosin alpha-1 FDA-approved?
| Record | Status | Source |
|---|---|---|
| FDA approval | No approved application Drugs@FDA returned no application for “thymalfasin”. | openFDA |
| Compounding: nominated, then withdrawn Thymosin-alpha 1 (Ta1) | Withdrawn nomination FDA still lists its safety concerns: “Compounded drugs containing thymosin-alpha-1 (Ta1) may pose significant risk for immunogenicity for certain routes of administration and may have complexities with regard to peptide-related impurities and API characterization. The safety-related information is inadequate for the agency to sufficiently understand the extent of any safety issues raised by the proposed compounded drug.” | 4 |
FDA lists "Thymosin-alpha 1 (Ta1)" among substances whose compounding nominations were withdrawn. It notes significant immunogenicity risk for certain routes, complexities with impurities and API characterization, and says the safety information is inadequate for FDA to understand the extent of any safety issues4. Drugs@FDA returned no application for thymalfasin.
What is still unknown?
- Whether any subgroup benefits in sepsis. TESTS found possible differences by age and diabetes, but these were subgroup analyses3.
- Trials outside China and Japan. The sepsis and hepatitis B trials we cite were run there3,1.
What effects has Thymosin alpha-1 shown, by body system?
Each row is graded separately using the Residue evidence scale: a compound can carry an A for one use and a D for another.
| System | What was observed | Grade |
|---|---|---|
| Sepsis (mortality) | No effect on 28-day mortality in a 1,106-patient phase 3 RCT3; a smaller single-blind RCT was marginal5. | B |
| Chronic hepatitis B | ALT normalization and HBV-DNA clearance in a 316-patient dose-comparison RCT; mixed results versus interferon1,6. | B |
| Immune markers | Greater mHLA-DR recovery in sepsis5; faster CD4+ recovery in COVID-197. | B |
| COVID-19 recovery | No significant difference in recovery in a 49-patient open-label trial7. | C |
How much research is there on Thymosin alpha-1?
| Phase | Studies | Breakdown |
|---|---|---|
| Early phase 1 | 1 | 1 completed, 0 active or recruiting, 0 stopped, 0 other |
| Phase 1 | 3 | 1 completed, 2 active or recruiting, 0 stopped, 0 other |
| Phase 2 | 31 | 9 completed, 10 active or recruiting, 5 stopped, 7 other |
| Phase 3 | 8 | 4 completed, 2 active or recruiting, 0 stopped, 2 other |
| Phase 4 | 10 | 5 completed, 0 active or recruiting, 0 stopped, 5 other |
| Not applicable | 10 | 3 completed, 4 active or recruiting, 0 stopped, 3 other |
| Observational | 2 | 1 completed, 1 active or recruiting, 0 stopped, 0 other |
Compare and continue
Questions readers ask
Is thymosin alpha-1 FDA-approved?
No. Drugs@FDA returned no application for thymalfasin at our last fetch, and FDA lists 'Thymosin-alpha 1 (Ta1)' among withdrawn compounding nominations, citing immunogenicity risk and inadequate safety information4.
Does thymosin alpha-1 work for sepsis?
The largest trial says no clear benefit: TESTS randomized 1,106 adults and found no difference in 28-day mortality3. Possible differences by age and diabetes were subgroup findings only.
References
Every source below was retrieved from its official API or page and cached on the data-edition date. Numbers match the margin notes.
- 1 PubMed Iino S, Toyota J, Kumada H, et al. The efficacy and safety of thymosin alpha-1 in Japanese patients with chronic hepatitis B; results from a randomized clinical trial. J Viral Hepat 2005. PMID 15850471; doi:10.1111/j.1365-2893.2005.00633.x.
- 2 PubMed Dominari A, Hathaway Iii D, Pandav K, et al. Thymosin alpha 1: A comprehensive review of the literature. World J Virol 2020. PMID 33362999; doi:10.5501/wjv.v9.i5.67.
- 3 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. PMID 39814420; doi:10.1136/bmj-2024-082583.
- 4 FDA Certain Bulk Drug Substances for Use in Compounding that May Present Significant Safety Risks. U.S. FDA, content current as of 04/22/2026.
- 5 PubMed 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. PMID 23327199; doi:10.1186/cc11932.
- 6 PubMed Yang YF, Zhao W, Zhong YD, et al. Comparison of the efficacy of thymosin alpha-1 and interferon alpha in the treatment of chronic hepatitis B: a meta-analysis. Antiviral Res 2008. PMID 18078676; doi:10.1016/j.antiviral.2007.10.014.
- 7 PubMed Shehadeh F, Benitez G, Mylona EK, et al. 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; doi:10.1093/infdis/jiac362.
- 8 PubChem PubChem compound record: Thymalfasin. C129H215N33O55 · MW 3108.3 g/mol.
- 9 ClinicalTrials.gov ClinicalTrials.gov registry search: thymosin alpha 1 OR thymalfasin. 65 registered studies at fetch.
- 10 PubMed Esposito S, Deventer K, Goeman J, et al. Synthesis and characterization of the N-terminal acetylated 17-23 fragment of thymosin beta 4 identified in TB-500, a product suspected to possess doping potential. Drug Test Anal 2012. PMID 22962027; doi:10.1002/dta.1402.