Summary
Thymosin alpha-1 (thymalfasin) is a synthetic copy of a 28 amino acid peptide from the thymus, the gland where immune T cells mature, that enhances T cell maturation and function. It is approved as Zadaxin in more than 30 countries, mainly in Asia and Europe, for chronic hepatitis B and as an immune adjuvant (a helper that strengthens immune responses, such as to vaccines), but it has never been approved by FDA. A randomized trial in chronic hepatitis B showed a higher rate of viral clearance at 18 months (41% versus 9%), while the largest sepsis trial (361 patients) found a mortality reduction that was not statistically significant, meaning it could have been chance. FDA placed it in 503A Category 2 (compounding ingredients flagged for significant safety risks) in 2023; the nomination has since been withdrawn, leaving no lawful US compounding pathway.
What is Thymosin alpha-1?
Thymosin alpha-1 is a 28 amino acid N-acetylated thymic peptide (synthetic form of a natural thymus derived immunomodulator). It is also known as Thymalfasin, Zadaxin, Ta1, T-alpha-1, Thymosin alpha 1 acetate.
How does it work?
Thymosin alpha-1 acts on toll-like receptors (TLR2 and TLR9) on dendritic cells and precursor T cells, promoting T cell differentiation, increasing IL-2 and interferon production, enhancing natural killer and CD8 cytotoxic activity, and reducing T cell exhaustion markers. It has no direct antiviral or antibacterial action; its effects come from immune restoration, which is why it has been studied in hepatitis, sepsis, and severe COVID-19.
| Cluster | Immune and antimicrobial |
|---|---|
| Routes | Subcutaneous injection (all trials and foreign labeling) |
| Conditions studied | Inflammation and inflammatory bowel disease; Immune support and immune deficiency |
| Record | v2, draft, verified Sep 22, 2026 |
What does the evidence say about Thymosin alpha-1?
Randomized trials exist but results are mixed and mostly from Asia. Chien 1998 (n = 98, chronic hepatitis B): 1.6 mg subcutaneously twice weekly for 26 weeks produced complete virological response in 40.6% versus 9.4% of untreated controls at 18 months, with histological improvement and no significant side effects. Wu 2013 ETASS (n = 361, severe sepsis): 28 day mortality was 26.0% with thymosin alpha-1 versus 35.0% with control, a relative risk of 0.74 that did not reach conventional significance (p = 0.062). Liu 2020 (n = 76, severe COVID-19, retrospective): mortality 11.1% versus 30.0% in treated versus untreated patients. Reviews by Camerini 2015 and Dominari 2020 summarize decades of use as an adjuvant with a consistently benign safety profile.
| Evidence type | Indexed studies | Participants (human) |
|---|---|---|
| Human randomized trials | 4 | 459 |
| Human observational studies | 1 | 76 |
| Animal studies | 0 | n/a |
| All indexed studies | 5 | 535 |
Human evidence
Chien 1998: 98 patients with chronic hepatitis B randomized to 26 weeks of therapy, 52 weeks of therapy, or no treatment; complete clearance of HBV DNA and HBeAg at 18 months occurred in 40.6%, 26.5%, and 9.4% respectively, and responses accumulated after therapy ended. Wu 2013: 361 ICU patients with severe sepsis in six Chinese hospitals randomized to thymosin alpha-1 1.6 mg twice daily for 7 days plus standard care or standard care alone; 28 day mortality 26.0% versus 35.0% (relative risk 0.74, 95% CI 0.54 to 1.02) with greater recovery of monocyte HLA-DR expression. Liu 2020: retrospective review of 76 severe COVID-19 cases in Wuhan; treated patients had 11.1% mortality versus 30.0%, with restoration of CD4 and CD8 counts and reduced PD-1 and Tim-3 exhaustion markers. Camerini 2015 and Dominari 2020 review roughly four decades of trials in hepatitis B and C, as a vaccine adjuvant in dialysis patients, and in cancer immunotherapy, noting consistent tolerability.
Animal evidence
Mouse and rat studies show thymosin alpha-1 restores T cell function after thymectomy, chemotherapy, or immunosuppression, improves survival in bacterial and fungal infection models, and acts through TLR signaling on dendritic cells. Animal data established the mechanism; the evidence base is human.
Key studies
| Study | Design and population | Outcome | Grade |
|---|---|---|---|
| Efficacy of thymosin alpha1 in patients with chronic hepatitis B: a randomized, controlled trial1998 PMID 9581695 | Randomized controlled trial with untreated control, 18 month follow upn = 98 Adults with chronic hepatitis B in Taiwan | Complete virological response at 18 months in 40.6% (26 week course) and 26.5% (52 week course) versus 9.4% of controls; histological improvement; no significant side effects | Evidence: Human RCT evidence |
| The efficacy of thymosin alpha 1 for severe sepsis (ETASS): a multicenter, single-blind, randomized and controlled trial2013 PMID 23327199 | Multicenter, single blind, randomized controlled trialn = 361 ICU patients with severe sepsis in China | 28 day mortality 26.0% versus 35.0% (relative risk 0.74, 95% CI 0.54 to 1.02, p = 0.062); improved monocyte HLA-DR recovery | Evidence: Human RCT evidence |
| Thymosin Alpha 1 Reduces the Mortality of Severe Coronavirus Disease 2019 by Restoration of Lymphocytopenia and Reversion of Exhausted T Cells2020 PMID 32442287 | Retrospective cohortn = 76 Patients with severe COVID-19 in Wuhan | Mortality 11.1% in treated versus 30.0% in untreated patients; restored T cell counts and reduced exhaustion markers | Evidence: Human observational evidence |
| Historical review of thymosin alpha 1 in infectious diseases2015 PMID 26098768 | Narrative reviewTrials in hepatitis B and C, vaccine adjuvant use, and other infections | Summarizes decades of clinical use and approvals in more than 30 countries with a benign safety profile | Evidence: Human RCT evidence |
| Thymosin alpha 1: A comprehensive review of the literature2020 PMID 33362999 | Narrative reviewHuman and preclinical studies across infection, cancer, and immunodeficiency | Summarizes mechanism, dosing regimens, and clinical evidence across indications | Evidence: Human RCT evidence |
Conditions studied
| Condition | Grade | Note |
|---|---|---|
| Inflammation and inflammatory bowel disease | Evidence: Human RCT evidence | Approved in several countries (not the US) for hepatitis B and as an immune adjuvant; trials in sepsis. |
| Immune support and immune deficiency | Evidence: Human RCT evidence | Improved hepatitis B viral response in a 98 patient trial; in severe sepsis (n = 361), 28 day mortality was 26.0% versus 35.0%, which was not statistically significant; FDA placed it in 503A Category 2 in 2023. |
Is Thymosin alpha-1 legal in the United States?
FDA and compounding status
Not FDA approved, although approved as Zadaxin (thymalfasin) in more than 30 countries. FDA placed thymosin alpha-1 in 503A Category 2 in 2023, citing immunogenicity risk and inadequate safety information for compounded product. FDA's Category 2 page (current as of April 22, 2026) now lists it under bulk drug substances nominated but withdrawn, so it is no longer in Category 2 but has no active nomination and is not on the 503A bulks list. That leaves US compounding pharmacies without a lawful basis to make it. It was not among the peptides reviewed by the advisory committee in July 2026.
WADA status
WADA status unclear. The current prohibited list does not name this compound explicitly and its class status is not settled. Athletes should ask their anti-doping organization before use.
Regulatory timeline
- FDA
FDA lists BPC-157 and 16 other peptides as withdrawn from 503A Category 2
FDA's Category 2 page, revised in April 2026 and current as of April 22, 2026, moved BPC-157, AOD-9604, CJC-1295, dihexa, DSIP, epitalon, injectable GHK-Cu, ipamorelin, KPV, LL-37, melanotan II, MOTS-c, PEG-MGF, selank, semax, thymosin alpha-1, and thymosin beta-4 fragment (TB-500) to a list of bulk drug substances nominated but withdrawn by their nominators. A withdrawn substance is no longer in 503A Category 2, but withdrawal is not an approval and does not place a substance on the 503A bulks list; a 503A pharmacy still needs a listing before it may compound it. Ipamorelin acetate remains in 503B Category 2. Seven of the withdrawn peptides (BPC-157, KPV, TB-500, MOTS-c, semax, epitalon, and DSIP) were taken to the Pharmacy Compounding Advisory Committee in July 2026.
- FDA
FDA places a batch of nominated peptides in 503A Category 2
In September 2023 FDA updated its 503A bulk drug substances category lists to place a group of nominated peptides in Category 2, which means FDA identified significant safety risks and the substances may not be used in 503A compounding while the evaluation continues. Kisspeptin-10 and ibutamoren (MK-677) were added on September 29, 2023 and remain in Category 2 on the FDA page current as of April 22, 2026. BPC-157, CJC-1295, ipamorelin, AOD-9604, dihexa, DSIP, epitalon, KPV, MOTS-c, selank, semax, melanotan II, LL-37, thymosin alpha-1, and thymosin beta-4 fragment (TB-500) were also placed in Category 2 under the 503A interim policy; that same page now lists them as nominated but withdrawn (see the April 2026 event). Hexarelin, PNC-27, and 5-amino-1MQ have never appeared on the FDA category lists.
Full tracker for Thymosin alpha-1 or the category-wide tracker.
What published studies of Thymosin alpha-1 used
Ranges below are reported from published studies and labeling only. PeptideAgent does not recommend doses or protocols.
Chronic hepatitis B (Chien 1998 and Zadaxin labeling abroad): 1.6 mg subcutaneously twice weekly for 6 to 12 months. Severe sepsis (Wu 2013): 1.6 mg subcutaneously twice daily for 7 days. Vaccine adjuvant studies: 1.6 mg twice weekly around vaccination. These are trial and foreign label doses; there is no US label.
Routes reported
| # | Route |
|---|---|
| 1 | Subcutaneous injection (all trials and foreign labeling) |
What are the side effects and interactions of Thymosin alpha-1?
Side effects
| # | Reported side effect |
|---|---|
| 1 | Injection site redness and discomfort (most common) |
| 2 | Transient muscle aches or flu like symptoms |
| 3 | No significant side effects in the hepatitis B trial and no serious drug related events in the sepsis trial |
| 4 | Immunogenicity risk from impurities in compounded product (FDA Category 2 rationale) |
Interactions
| # | Interaction |
|---|---|
| 1 | Immunosuppressants (corticosteroids, calcineurin inhibitors, biologics): thymosin alpha-1 aims to increase immune activity and could oppose them; no formal interaction studies |
| 2 | Interferon alfa: combined regimens have been studied in hepatitis and appear tolerable |
| 3 | Vaccines: used deliberately as an adjuvant to improve responses in immunocompromised patients |
Contraindications
| # | Contraindication |
|---|---|
| 1 | Deliberate immunosuppression, such as after organ transplant (theoretical, from mechanism) |
| 2 | Known hypersensitivity |
| 3 | Pregnancy and breastfeeding (no data) |
| 4 | Autoimmune disease has not been studied and warrants caution |
How do people access Thymosin alpha-1 legally?
Typical cost: Not available through licensed US channels since the 2023 Category 2 placement. Zadaxin is sold by prescription in countries where it is approved.
Verified access options
Step 1
No lawful United States access path identified on the last verified date; the 503A nomination was withdrawn and it is not on the bulks list.
Step 2
Not available as an FDA approved product in the United States, although approved abroad as Zadaxin (thymalfasin).
Step 3
Products labeled research use only are not lawful for human use and are not verified for identity or purity.
Access paths are verified against public regulatory records and prescriber licensing. We never list unlicensed vendors.
Compare Thymosin alpha-1
What's actually offered, and what that means for you
Licensed compounding pharmacies, clinics, and telehealth prescribers openly offer many unapproved peptides, and prescribers write prescriptions for them. That does not make thymosin alpha-1 lawful. Thymosin alpha-1 is not FDA approved and not on the 503A bulks list, so a pharmacy has no lawful basis to compound it. [6] [7]
Enforcement is uneven. FDA mostly acts through warning letters to compounders and online sellers, Category 2 safety listings, and import alerts that let it detain shipments, rather than stopping every pharmacy. State pharmacy boards oversee pharmacies day to day, and their rules differ. [6] [10] [11] [12] [13]
What changes for you
- No FDA review of the product: FDA does not check a compounded drug's safety, effectiveness, or quality before it is sold. [13]
- Identity, purity, sterility, and dose accuracy can vary from batch to batch. [6]
- Insurance rarely covers it, so you usually pay cash.
- For tested athletes, WADA status is unclear; ask your anti-doping organization before any use. [9]
What to check
These checks lower some risks, but they do not make an unlawfully compounded product lawful or safe. Check for:
- A 503A pharmacy licensed in your state (your state board of pharmacy publishes license lookups). [13]
- A real evaluation by a licensed prescriber, not just an online form.
- A certificate of analysis for the specific batch.
Frequently asked questions
Is thymosin alpha-1 legal in the United States?
It is not FDA approved and cannot currently be compounded lawfully. FDA placed it in 503A Category 2 (compounding ingredients flagged for significant safety risks) in 2023; the nomination was later withdrawn, which removes it from Category 2 but also leaves it off the 503A bulks list (ingredients pharmacies may use to compound drugs for individual patients), so pharmacies have no lawful basis to compound it. It is a prescription drug (Zadaxin) in more than 30 other countries. Possession is not a crime; research chemical products are not for human use. [4] [6] [7]
Does thymosin alpha-1 work for hepatitis B?
In a 98 patient randomized trial, a 26 week course of 1.6 mg twice weekly produced complete virological response (loss of HBV DNA and HBeAg) in 40.6% of patients versus 9.4% of untreated controls when assessed at 18 months, with histological improvement and no significant side effects. That is the basis of its approval abroad. It is now rarely used in the West because nucleoside antivirals are more effective and oral. [1] [4]
Does thymosin alpha-1 help sepsis or severe infections?
Possibly, but not proven. In the 361 patient ETASS trial, 28 day mortality in severe sepsis was 26.0% with thymosin alpha-1 versus 35.0% with standard care, a relative risk of 0.74 that missed statistical significance (p = 0.062). A retrospective study of 76 severe COVID-19 patients found lower mortality (11.1% versus 30.0%) in treated patients, but retrospective data cannot establish cause. Larger confirmatory trials are needed. [2] [3]
What are the side effects of thymosin alpha-1?
Few. Injection site redness and discomfort are the most common, with occasional transient muscle aches. The hepatitis B trial reported no significant side effects and the sepsis trial no serious drug related events. FDA's Category 2 concern was about immunogenicity and impurities in compounded product rather than the molecule's clinical record. [1] [2] [6]
How is thymosin alpha-1 taken?
By subcutaneous injection. Hepatitis B regimens use 1.6 mg twice weekly for 6 to 12 months, the sepsis trial used 1.6 mg twice daily for 7 days, and vaccine adjuvant studies used 1.6 mg twice weekly around vaccination. These are trial and foreign label doses; there is no US label. [1] [2] [5]
How much does thymosin alpha-1 cost?
It is not currently available through licensed US channels. Zadaxin is available by prescription in countries where it is approved. [6]
Is thymosin alpha-1 banned by WADA?
It is not named on the WADA Prohibited List. Because it is approved by health authorities in many countries, the S0 non-approved substance rule does not clearly apply, and it is not a growth factor or hormone in the S2 sense. PeptideAgent marks it unclear; athletes should ask their anti-doping organization before use. [9]
Thymosin alpha-1 vs TB-500 (thymosin beta-4): what is the difference?
They share a name and nothing else. Thymosin alpha-1 is an immune modulator with decades of human trials and approvals abroad. TB-500 is a fragment of thymosin beta-4, a cell migration protein studied for tissue repair, with no human RCT data. TB-500 was recommended for the 503A bulks list by FDA's advisory committee in July 2026; thymosin alpha-1 was not reviewed. [5] [8]
Decisions about starting, stopping, or combining any treatment belong with a licensed clinician who knows your history.
From the blog
- Thymosin alpha-1 access: approved abroad, not in the US
Thymosin alpha-1 is approved as Zadaxin in more than 30 countries but has never been FDA approved, and US compounding has no lawful basis. What that means for access, forms, and thymalin.
Sources
Numbered citations above point to these primary sources. PubMed entries link to the indexed abstract.
- [1]Chien RN et al. Efficacy of thymosin alpha1 in patients with chronic hepatitis B: a randomized, controlled trial. Hepatology 1998PubMed 9581695, 1998
- [2]Wu J et al. The efficacy of thymosin alpha 1 for severe sepsis (ETASS): a multicenter, single-blind, randomized and controlled trial. Crit Care 2013PubMed 23327199, 2013
- [3]Liu Y et al. Thymosin alpha 1 reduces the mortality of severe COVID-19 by restoration of lymphocytopenia and reversion of exhausted T cells. Clin Infect Dis 2020PubMed 32442287, 2020
- [4]Camerini R, Garaci E. Historical review of thymosin alpha 1 in infectious diseases. Expert Opin Biol Ther 2015PubMed 26098768, 2015
- [5]Dominari A et al. Thymosin alpha 1: A comprehensive review of the literature. World J Virol 2020PubMed 33362999, 2020
- [6]FDA: Certain bulk drug substances for use in compounding may present significant safety risks (Category 2 list and withdrawn nominations, content current as of April 22, 2026)FDA, 2026
- [7]FDA: Bulk drug substances used in compounding under section 503A of the FD&C ActFDA, 2026
- [8]FDA: July 23-24, 2026 meeting of the Pharmacy Compounding Advisory Committee (BPC-157, KPV, TB-500, MOTS-c, DSIP, semax, epitalon)FDA, 2026
- [9]WADA Prohibited ListWADA, 2026
- [10]FDA: Compounding inspections, recalls, and other actions (warning letters to compounders)FDA
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PeptideAgent. (2026, September 22). Thymosin alpha-1: evidence, legality, and access. https://peptideagent.ai/peptides/thymosin-alpha-1- HTML link
<a href="https://peptideagent.ai/peptides/thymosin-alpha-1">Thymosin alpha-1: evidence, legality, and access</a>, PeptideAgent, updated September 22, 2026.