Thymosin Alpha-1

In simple words

Thymosin alpha-1 is a natural 28-amino-acid hormone of the thymus gland, sold as the drug Zadaxin in many countries. It is studied as an agent that helps the immune system fight infections and tumors while also calming excessive inflammation.

What this molecule is

28 amino acids: Ac-Ser-Asp-Ala-Ala-Val-Asp-Thr-Ser-Ser-Glu-Ile-Thr-Thr-Lys-Asp-Leu-Lys-Glu-Lys-Lys-Glu-Val-Val-Glu-Glu-Ala-Glu-Asn-OH. N-acetylserine. ~3108 Da. Natural thymic hormone.

Why it is studied

Registered in 35+ countries (Zadaxin, SciClone). Phase III RCT in COVID-19: mortality 11.1% vs 38.5% with placebo. Meta-analysis of 8 studies: RR 0.59. Approved for hepatitis B and C, immunodeficiencies, and as adjuvant therapy in cancer. TESTS trial, BMJ 2025 (n=1106): sepsis — negative primary outcome, positive subgroup analysis in older adults/people with diabetes.

How it works

Toll-like receptors TLR2/TLR9 on dendritic cells → ↑DC maturation → ↑antigen presentation → ↑Th1 response (IFN-γ, IL-2) + ↑CD8+ cytotoxic T cells. ↑NK cells. ↑IDO (indoleamine 2,3-dioxygenase) → ↓excessive inflammation. Bidirectional regulation: in immunosuppression it ↑immunity; in hyperinflammation it ↓cytokine storm.

Doses used in studies

Studies and the Zadaxin prescribing information used a fixed dose of 1.6 mg SC twice a week. For hepatitis B — a course of 6–12 months; as adjuvant therapy in cancer — long-term.

Combined with in studies

• Checkpoint inhibitors — anti-PD-1/PD-L1 — synergy in oncology
• Interferon-α — hepatitis B — standard combination
• Vaccines — ↑immune response in older adults

Level of evidence

Level A Human clinical trials. There are randomized controlled trials (RCTs), or the compound has been approved by a regulatory agency. The most reliable level. Registered in 35+ countries. Phase III RCT. Meta-analyses.

Important to know

⚠️ Not FDA-approved. The TESTS trial (BMJ 2025) was formally negative in sepsis. COVID Phase III — small sample (n=105). Prescription drug, not Research only.

Studies in PubMed

1. A Double-blind Multicenter Two-arm Randomized Placebo-controlled Phase-III Clinical Study to Evaluate the Effectiveness and Safety of Thymosin α1 as an Add-on Treatment to Existing Standard of Care Treatment in Moderate-to-severe COVID-19 Patients. (Indian J Crit Care Med, 2022)
2. The efficacy of thymosin alpha-1 therapy in moderate to critical COVID-19 patients: a systematic review, meta-analysis, and meta-regression. (Inflammopharmacology, 2023)
3. The efficacy and safety of thymosin α1 for sepsis (TESTS): multicentre, double blinded, randomised, placebo controlled, phase 3 trial. (BMJ, 2025)
4. Thymosin alpha 1 - Reimagine its broader applications in the immuno-oncology era. (Int Immunopharmacol, 2023)
5. Thymosin alpha 1 restores the immune homeostasis in lymphocytes during Post-Acute sequelae of SARS-CoV-2 infection. (Int Immunopharmacol, 2023)
6. A first-in-human, randomized, double-blind, single- and multiple-dose, phase I study of recombinant human thymosin β4 in healthy Chinese volunteers. (J Cell Mol Med, 2021)