Thymosin Alpha-1 (Thymalfasin / Zadaxin)
Thymosin Alpha-1 (thymalfasin / Zadaxin) — evidence & status

Class: peptide
Synonyms: Thymosin Alpha-1
Tα1
thymalfasin
INN thymalfasin
brand Zadaxin
a thymic immune peptide. INCI: none
Function tags: immune modulation
antiviral (hepatitis)
vaccine adjuvant
(studied:) sepsis, cancer, COVID-19
Overall evidence grade: B
WADA prohibited: no
WADA note: Sport: Tα1 is not on the WADA Prohibited List — unlike its "cousin" TB-500 (#12), which is banned.
Last updated: 2026-07-13

In brief: Thymosin Alpha-1 (thymalfasin / Zadaxin) is a 28-amino-acid thymic immune-modulating peptide and one of the most clinically validated peptides in this register — approved in ~35 countries, with a 2024 review documenting >30 clinical trials in >11,000 people. Its strongest evidence is chronic hepatitis B and immune modulation. It is not FDA-approved for marketing in the US (orphan designations and Phase 3 that stalled commercially, not on safety), and its US compounding status has been unsettled. The general "immune-boosting" wellness use is extrapolated. It is distinct from the tissue-repair peptide TB-500 (#12) despite the shared "thymosin" name.

## Identity a **28-amino-acid**, N-terminally acetylated peptide (~3,108 Da; < 40 aa → peptide), a fragment of **prothymosin alpha**, produced by thymic epithelial and peripheral immune cells. Its international non-proprietary name (INN) is **thymalfasin**, and it has been marketed as **Zadaxin**. Serum levels **decline ~40–60% with age** (thymic involution). Discovered by **Allan Goldstein's lab at George Washington University** (Goldstein et al., 1977) — **the same lab associated with thymosin beta-4 / TB-500 (#12)** — but Tα1 and Tβ4 have **fundamentally different biology** (Tα1 = immune modulator; Tβ4 = actin-sequestering tissue repair). ## Development & history - Isolated by Goldstein's group in the 1970s from thymic tissue (thymosin fraction 5) — one of the first demonstrations that the thymus secretes soluble immune-modulating factors. **Synthetic** Tα1 was made by solid-phase synthesis in the early 1980s, freeing production from tissue extraction.
- **SciClone Pharmaceuticals** developed the synthetic version as **Zadaxin** and pursued international approvals: **China approved it for hepatitis B in 1996**, and it went on to marketing authorisation in **~35–37 countries** across Asia, South America, the Middle East and parts of Europe.
- **US:** the FDA granted **orphan-drug *designations*** (hepatitis B in 1991, plus melanoma, DiGeorge anomaly, hepatocellular carcinoma), and SciClone ran US **Phase 3** trials (hepatitis C, melanoma) — but these **did not lead to US marketing approval.** (Widely attributed to commercial/regulatory economics, not a safety signal.) ## Mechanism (as proposed) an **immune modulator** acting largely through **Toll-like receptors TLR2 and TLR9** on dendritic and myeloid antigen-presenting cells → activates **T-cell / cell-mediated immunity.** It promotes T-cell maturation (upregulating CD3/CD4/CD8), dendritic-cell maturation and **Th1** polarisation, and enhances **NK-cell** function, helping restore immune competence in immunosuppressed states while also contributing to control of inflammation and tolerance.

Evidence grades by outcome:
outcome: Chronic hepatitis B (approved indication)
grade: B
base: Pivotal trials; approved in ~35 countries; part of a >30-trial / >11,000-subject database
effect: Antiviral / immune benefit
caveat: Strongest use; approved widely but not FDA-approved (US)
outcome: Immune modulation / vaccine response (elderly, immunocompromised)
grade: B
base: RCTs (co-administration with influenza, hep B, COVID vaccines)
effect: Improved antibody titres / durability
caveat: Benefit clearest in immunocompromised; context-dependent
outcome: Sepsis
grade: C
base: Multiple RCTs + systematic review/meta-analysis
effect: Suggestive / mixed
caveat: Aggregate evidence re-evaluated; context-dependent
outcome: Cancer immunotherapy adjunct
grade: C
base: >40 adjuvant trials (melanoma, HCC, NSCLC); 2006 NSCLC (n=95, +21% 12-mo survival)
effect: Mixed
caveat: Adjuvant use; results mixed across cancers
outcome: COVID-19 (severe/hospitalised)
grade: C
base: Zhang 2020 (China); Shehadeh 2023 US pilot (hypoxemia + lymphocytopenia)
effect: Encouraging but preliminary
caveat: Observational/pilot; not definitive
outcome: General "immune boosting" (healthy people / wellness)
grade: D
base: Extrapolated from mechanism + age-related decline
effect: Plausible
caveat: Not proven for healthy-person immune enhancement
outcome: Safety
base: Millions treated; approved-drug record
effect: Excellent
caveat: Very well tolerated; minimal side effects

Legal status:
region: US
status: Not FDA-approved (under review)
note: not FDA-approved for marketing (orphan designations + stalled Phase 3). Historically dispensed via 503A/503B compounding; its compounding status has been in flux through the 2023–2026 FDA peptide review — confirm current status.
region: EU
status: not EMA-centrally approved (used in some countries' clinical
note: not EMA-centrally approved (used in some countries' clinical practice/trials).

Cosmetic claims:

Note: Reference entry — not sold here. The strong-evidence immune peptide and a deliberate contrast to DSIP (#45): where DSIP is "50 years, still unproven," Thymosin Alpha-1 is approved in ~35 countries with a large clinical database. A prescription/compounded drug, not a wellness supplement. No dosing published here.
Status note: US compounding status evolving — re-check

Sources:
Goldstein AL, Low TL, et al. (Isolation and characterisation of thymosin alpha-1.) 1977.
Romani L, et al. (Dendritic-cell maturation / Th1 polarisation; TLR mechanism.) 2004.
Zadaxin (thymalfasin) pivotal hepatitis-B / hepatitis-C trials; sepsis RCT meta-analysis.
Shehadeh F, et al. A pilot trial of thymalfasin (thymosin-alpha-1) in hospitalised COVID-19 patients with hypoxemia and lymphocytopenia. J Infect Dis. 2023.
Comprehensive review (2024) — >30 clinical trials, >11,000 subjects; PMC7747025 (literature review).