# Thymosin alpha-1 - Canonical: https://residue.info/c/thymosin-alpha-1/ - Also called: Thymalfasin, Tα1, Ta1, Zadaxin - Evidence grade: B (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. - Status: Not FDA-approved · FDA compounding nomination withdrawn - PubChem CID: 16130571 - Updated: 2026-10-19 · Reviewed by: Residue Editorial Team Thymosin alpha-1 (thymalfasin) is a 28-amino-acid thymic peptide studied as an immune modulator [1][2]. Its largest trial, TESTS, randomized 1,106 adults with sepsis and found no difference in 28-day mortality (23.4% versus 24.1%) [3]. Hepatitis B trials reported viral and liver-enzyme responses [1]. It is not FDA-approved, and its compounding nomination was withdrawn [4]. ## 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 differed [3]. (anchor: https://residue.info/c/thymosin-alpha-1/#kf-pmid-39814420) - The earlier single-blind ETASS trial (361 patients with severe sepsis) reported 26.0% versus 35.0% mortality with a marginal P value [5]. (anchor: https://residue.info/c/thymosin-alpha-1/#kf-pmid-23327199) - 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 stopping [1]. (anchor: https://residue.info/c/thymosin-alpha-1/#kf-pmid-15850471) - A meta-analysis of four RCTs (199 patients) found Tα1 inferior to interferon alpha at end of treatment but superior six months after treatment [6]. (anchor: https://residue.info/c/thymosin-alpha-1/#kf-pmid-18078676) - In a 49-patient open-label COVID-19 trial, clinical recovery was not significantly improved, though CD4+ T-cell counts rose faster [7]. (anchor: https://residue.info/c/thymosin-alpha-1/#kf-pmid-36056913) ## Effects by system - Sepsis (mortality) (grade B): No effect on 28-day mortality in a 1,106-patient phase 3 RCT [3]; a smaller single-blind RCT was marginal [5]. (anchor: https://residue.info/c/thymosin-alpha-1/#effect-sepsis-mortality) - Chronic hepatitis B (grade B): ALT normalization and HBV-DNA clearance in a 316-patient dose-comparison RCT; mixed results versus interferon [1][6]. (anchor: https://residue.info/c/thymosin-alpha-1/#effect-chronic-hepatitis-b) - Immune markers (grade B): Greater mHLA-DR recovery in sepsis [5]; faster CD4+ recovery in COVID-19 [7]. (anchor: https://residue.info/c/thymosin-alpha-1/#effect-immune-markers) - COVID-19 recovery (grade C): No significant difference in recovery in a 49-patient open-label trial [7]. (anchor: https://residue.info/c/thymosin-alpha-1/#effect-covid-19-recovery) ## 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 function [2]. Thymalfasin, its synthetic form, is a 28-amino-acid polypeptide [1][7]; PubChem lists the formula C129H215N33O55 [8]. ## How is thymosin alpha-1 thought to work? It is classed as an immunomodulatory drug [3]. Reviews describe uses in immunocompromised states and malignancies, as a vaccine-response enhancer, and in sepsis and infections [2]. In trials, the measurable effects have been on immune markers: monocyte HLA-DR in sepsis [5] and CD4+ T-cell counts in COVID-19 [7]. ## 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 mortality [3]. **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 mild [1]. A meta-analysis of four small RCTs found Tα1 less effective than interferon alpha at the end of treatment but more effective six months later [6]. **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 oxygen [7]. **Registered trials.** ClinicalTrials.gov lists dozens of studies, many in sepsis, lung cancer and liver disease [9]. 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 issues [4]. 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 analyses [3]. - **Trials outside China and Japan.** The sepsis and hepatitis B trials we cite were run there [3][1]. ## Frequently asked questions **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 information [4]. **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 mortality [3]. Possible differences by age and diabetes were subgroup findings only. **What is thymalfasin?** Thymalfasin is the synthetic form of thymosin alpha-1 [7]. PubChem lists Zadaxin as a synonym [8]. **Is thymosin alpha-1 the same as thymosin beta-4 or TB-500?** No. Thymosin alpha-1 is a 28-residue immune peptide [1]; TB-500 is a seven-residue fragment of thymosin β4, a different protein [10]. ## Sources [1] The 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. https://pubmed.ncbi.nlm.nih.gov/15850471/ [2] Thymosin alpha 1: A comprehensive review of the literature. Dominari A et al. World J Virol. 2020. https://pubmed.ncbi.nlm.nih.gov/33362999/ [3] The efficacy and safety of thymosin α1 for sepsis (TESTS): multicentre, double blinded, randomised, placebo controlled, phase 3 trial. Wu J et al. BMJ. 2025. https://pubmed.ncbi.nlm.nih.gov/39814420/ [4] Certain Bulk Drug Substances for Use in Compounding that May Present Significant Safety Risks. U.S. FDA, content current as of 04/22/2026. https://www.fda.gov/drugs/human-drug-compounding/certain-bulk-drug-substances-use-compounding-may-present-significant-safety-risks [5] The efficacy of thymosin alpha 1 for severe sepsis (ETASS): a multicenter, single-blind, randomized and controlled trial. Wu J et al. Crit Care. 2013. https://pubmed.ncbi.nlm.nih.gov/23327199/ [6] Comparison 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. https://pubmed.ncbi.nlm.nih.gov/18078676/ [7] A 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. https://pubmed.ncbi.nlm.nih.gov/36056913/ [8] PubChem compound record: Thymalfasin. C129H215N33O55 · MW 3108.3 g/mol. https://pubchem.ncbi.nlm.nih.gov/compound/16130571 [9] ClinicalTrials.gov registry search: thymosin alpha 1 OR thymalfasin. 65 registered studies at fetch. https://clinicaltrials.gov/search?intr=thymosin%20alpha%201%20OR%20thymalfasin [10] 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. Esposito S et al. Drug Test Anal. 2012. https://pubmed.ncbi.nlm.nih.gov/22962027/ --- From Residue. Research and education only; not medical advice. Quote with attribution and a link to the canonical page.