Thymosin Alpha 1: Safety Profile & Research Summary
24 PubMed CitationsExpert ReviewedGMP CertifiedLast Reviewed: February 2026
Clinical Trials
✅ Thymosin Alpha 1 is one of the most clinically studied peptides in existence, with 10+ completed clinical trials and approval in 30+ countries as Zadaxin (thymalfasin).
| Trial | Phase | n= | Indication | Key Result | Outcome |
|---|---|---|---|---|---|
| ETASS | Phase 3 | 361 | Severe sepsis | 26% vs 35% mortality (P=0.049) | ✅ Positive |
| TESTS | Phase 3 | 1,106 | Sepsis | No mortality benefit | ❌ Negative |
| US HBV | Phase 3 | 99 | Hepatitis B | 25% vs 13% (not significant) | ❌ Negative |
| Japan HBV | RCT | 316 | Hepatitis B | 36.4% ALT normalization | ✅ Positive |
| HCV Triple | RCT | 552 | Hepatitis C | 41% SVR vs 26.3% (P<0.05) | ✅ Positive |
| Wuhan COVID | Retro | 76 | Severe COVID-19 | 11.1% vs 58.8% mortality | ✅ Positive |
| Melanoma | Phase 2 | 488 | Metastatic melanoma | 9.4 vs 6.6 mo OS (P=0.08) | ✅ Trend |
| NIBIT-M4 | F/U | 95 | Melanoma + Ipilimumab | 38.4 vs 8 mo OS (P=0.006) | ✅ Positive |
| GASTO-1043 | Phase 2 | 196 | NSCLC + chemoRT | 14.5% vs 35.4% pneumonitis | ✅ Positive |
| H1N1 Vaccine | Pilot | 122 | Hemodialysis study subjects | 89% vs 53% seroconversion | ✅ Positive |
Preclinical Animal Data (Selected)
- Lung Cancer (LLC/H460): 0.25 mg/kg SC × 11 days — 40.5% tumor volume inhibition (LLC), 21.9% inhibition (H460). Promoted CD4+/CD8+ T cell infiltration. [22]
- Melanoma (B16F10): Monotherapy reduced lung metastases by 32% (P<0.05); tumor growth decreased 34–46% (P=0.001–0.015). [5]
- Lung Adenoma Prevention: 0.4 mg/kg SC daily — reduced adenoma multiplicity by ~45% at 2.5 months.
- Leukemia/Carcinoma Combo: Tα1 (200 µg/kg) + IL-2/IFN + cyclophosphamide achieved complete tumor regression in FLC and 3LL models. [23]
- Sepsis (CLP): Tα1 + dexamethasone achieved highest survival rate; reversed DC depletion.
- Immunosuppression: 100–1,000× more active than thymosin fraction 5 in restoring immunity in 5-FU models.
- Aging: Restored antibody and T-cell responses in aged mice (23–24 months) to levels comparable to young animals. [24]
- Arthritis (CIA): 0.25–1 mg/kg reduced paw volume, weight, and arthritic scores.
Reported Tolerability Profile
Tα1 is consistently reported as well-tolerated across 2,000+ clinical subjects. [1]
- Common: Local injection site discomfort/redness (most frequent)
- Rare: Fever, fatigue, muscle aches, nausea (usually when combined with IFN)
- Hepatic: Transient ALT flares in HBV research application (often a sign of experimental effect)
- Serious (rare): Fatal immune hemolytic anemia and engraftment failure in HSCT recipients
- Preclinical: Single doses up to 20 mg/kg and 13-week repeated doses up to 6 mg/kg/day showed no adverse reactions
Contraindications: Hypersensitivity to Tα1; organ transplant recipients (risk of rejection/GVHD via immune stimulation). [1]
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References
- Dominari A, Hathaway III D, Pandav K, et al. Thymosin alpha 1: A comprehensive review of the literature. World J Virol, 9(5), 67-78, 2020.
- Goldstein AL, Low TL, McAdoo M, et al. Thymosin alpha1: Isolation and sequence analysis of an immunologically active thymic polypeptide. Proc Natl Acad Sci USA, 74(2), 725-729, 1977.
- Li J, Liu CH, Wang FS. Thymosin alpha 1: biological activities, applications and genetic engineering production. Peptides, 31(11), 2151-2158, 2010.
- Romani L, Bistoni F, Gaziano R, et al. Thymosin alpha 1 activates dendritic cells for antifungal Th1 resistance through toll-like receptor signaling. Blood, 103(11), 4232-4239, 2004.
- King R, Tuthill C. Immune Modulation with Thymosin Alpha 1 research application. Vitamins and Hormones, 102, 151-178, 2016.
- Pica F, Chimenti MS, Gaziano R, et al. Serum thymosin alpha 1 levels in study subjects with chronic inflammatory autoimmune diseases. Clin Exp Immunol, 186(1), 39-45, 2016.
- FDA. Certain Bulk Drug Substances for Use in Compounding that May Present Significant Tolerability Concerns. U.S. Food and Drug Administration, 2025.
- Elizondo-Riojas MA, Chamow SM, Tuthill CW, et al. NMR structure of human thymosin alpha-1. Biochem Biophys Res Commun, 416(3-4), 356-61, 2011.
- Billich A. Thymosin alpha1. SciClone Pharmaceuticals. Curr Opin Investig Drugs, 3(5), 698-707, 2002.
- Garaci E. Thymosin alpha1: a historical overview. Ann N Y Acad Sci, 1112, 14-20, 2007.
- Tao N, Xu X, Ying Y, et al. Thymosin alpha1 and Its Role in Viral Infectious Diseases: The Mechanism and Clinical Application. Molecules, 28(8), 3539, 2023.
- Romani L, Bistoni F, Perruccio K, et al. Thymosin alpha1 activates dendritic cell tryptophan catabolism and establishes a regulatory environment for balance of inflammation and tolerance. Blood, 108(7), 2265-74, 2006.
- Serafino A, Pica F, Andreola F, et al. Thymosin alpha1 Activates Complement Receptor-Mediated Phagocytosis in Human Monocyte-Derived Macrophages. J Innate Immun, 6(1), 72-88, 2014.
- Maio M, Mackiewicz A, Testori A, et al. Large randomized study of thymosin alpha 1, interferon alfa, or both in combination with dacarbazine in study subjects with metastatic melanoma. J Clin Oncol, 28(10), 1780-1787, 2010.
- Costantini C, Bellet MM, Pariano M, et al. A Reappraisal of Thymosin Alpha1 in Cancer Therapy. Front Oncol, 9, 873, 2019.
- 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. Critical Care, 17(1), R8, 2013.
- Liu Y, Pan Y, Hu Z, et al. Thymosin alpha-1 Reduces the Mortality of Severe Coronavirus Disease 2019 by Restoration of Lymphocytopenia and Reversion of Exhausted T Cells. Clin Infect Dis, 71(16), 2150-2157, 2020.
- Matteucci C, Grelli S, Balestrieri E, et al. Thymosin alpha 1 and HIV-1: recent advances and future perspectives. Future Microbiol, 12, 141-155, 2017.
- Carraro G, Naso A, Montomoli E, et al. Thymosin-alpha 1 (Zadaxin) enhances the immunogenicity of an adjuvanted pandemic H1N1v influenza vaccine. Vaccine, 30(11), 2001-2004, 2012.
- Romani L, Oikonomou V, Moretti S, et al. Thymosin alpha1 represents a potential potent single-molecule-based experimental protocol for cystic fibrosis. Nat Med, 23(5), 590-600, 2017.
- Pica F, Chimenti MS, Gaziano R, et al. Serum thymosin alpha 1 levels in chronic inflammatory autoimmune diseases. Clin Exp Immunol, 186(1), 39-45, 2016.
- Peng R, Xu C, Zheng H, et al. Modified Thymosin Alpha 1 Distributes and Inhibits the Growth of Lung Cancer in Vivo. ACS Omega, 5(18), 10374-10381, 2020.
- Garaci E, Mastino A, Pica F, Favalli C. Combination research application using thymosin alpha 1 and interferon after cyclophosphamide is able to experimental endpoint Lewis lung carcinoma in mice. Cancer Immunol Immunother, 36(5), 355-359, 1993.
- Simonova MA, Ivanov I, Shoshina NS, et al. Aging and Thymosin Alpha-1. Int J Mol Sci, 26(23), 11470, 2025.
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