Thymosin alpha 1 (Ta1) is a 28-amino-acid, N-terminally acetylated peptide first isolated from calf thymus in 1977 (Goldstein et al. 1977); in the body it corresponds to the first 28 residues of the larger protein prothymosin alpha. Its synthetic drug form, thymalfasin (sold abroad as Zadaxin), has been tested in randomized trials in hepatitis B, hepatitis C, cancer and sepsis, but the FDA has not approved any product containing it (FDA 2024). Thymalin, by contrast, is a polypeptide extract of calf thymus developed in Russia, with a much smaller and largely unreplicated evidence base. The comparison below is mostly about thymosin alpha 1, because that is where most of the trial data sits.
Both compounds are available for laboratory work: thymosin alpha 1 research peptide and thymalin. For a full treatment of thymalin’s origins and the Russian literature, see our thymalin research guide. This article focuses on how the two compare.
Allan Goldstein’s group reported the sequence of thymosin alpha 1 in 1977, describing “a heat stable, highly acidic molecule composed of 28 amino acid residues” isolated from calf thymus and present in a preparation called thymosin fraction 5 (Goldstein et al. 1977). FDA’s 2024 review gives its molecular weight as 3108.3 g/mol and notes that the chemically produced drug thymalfasin is identical in sequence to the natural peptide (FDA 2024).
For years it was unclear whether thymosin alpha 1 existed naturally or was a breakdown artifact of extraction. A 2003 study showed that the lysosomal enzyme legumain cleaves prothymosin alpha between Asn28 and Gly29 to release thymosin alpha 1, and that the peptide is present free in the cytosol of several mammalian tissues (Sarandeses et al. 2003).
The FDA review states that thymosin alpha 1 has immunomodulatory properties “mediated at least in part by its interactions with Toll-like receptor 9 (TLR9) on dendritic and lymphoid progenitor cells” (FDA 2024). FDA’s summary of published rodent studies says Ta1 “suppressed tumor growth, suppressed viral infections, and decreased sepsis” in in vivo models, while noting that most of those studies used doses well above those tested in people (FDA 2024).
In healthy men given a subcutaneous injection, thymosin alpha 1 reached peak serum levels at about 2 hours and had a serum half-life of about 2 hours, with no accumulation when given daily for 5 days in that study (Rost et al. 1999, as summarized by FDA 2024). After intravenous injection in rats, the half-life was only 1.9-3 minutes (FDA 2024).
The FDA states directly that it “has approved no drug products containing Ta1.” Its 2024 review also notes that thymosin alpha 1 is not approved in the United States, Japan or Europe, except Italy (FDA 2024).
SciClone Pharmaceuticals, which markets Zadaxin, reported approvals in countries across the Asia-Pacific region, Latin America, Eastern Europe and the Middle East for uses including hepatitis B and C and as a vaccine or chemotherapy adjuvant. FDA said it was “unable to independently verify these claims of approval in all the specified countries” (FDA 2024).
Orphan designation is a status granted to support development for rare conditions. It is not an approval. The FDA orphan database lists thymalfasin, sponsored by SciClone, as designated for:
Secondary sources mention other orphan designations for thymalfasin; we list only the two records we confirmed directly in the FDA database.
In December 2024, FDA staff presented thymosin alpha 1 to its Pharmacy Compounding Advisory Committee. After reviewing 12 proposed uses, from hepatitis B to chronic fatigue syndrome, FDA reported a “lack of evidence to support the effectiveness” of Ta1 “for the evaluated uses” and concluded that the evidence, safety information and characterization data “weigh against” adding it to the list of bulk substances allowed in 503A compounding (FDA 2024). The review found that neither the free base nor the acetate salt was well characterized, citing gaps in impurity, aggregate and endotoxin data and a potential immunogenicity risk.
The table summarizes the larger controlled trials. Doses are listed only to describe what each study tested.
| Trial | Setting and design | Patients | Main finding |
|---|---|---|---|
| Mutchnick 1999 | Chronic hepatitis B; phase 3, multicentre, double-blind, placebo-controlled; 1.6 mg twice weekly for 6 months | 97 | Complete response 14% vs 4% with placebo (P = 0.084); authors said results “do not confirm” earlier efficacy reports |
| Ciancio 2012 | Chronic hepatitis C in prior non-responders to peginterferon and ribavirin; randomized, placebo-controlled, added to peginterferon alfa-2a and ribavirin for 48 weeks | 552 | Sustained virologic response 12.7% vs 10.5% (P = 0.407) |
| ETASS 2013 | Severe sepsis; 6 hospitals in China; single-blind, no placebo | 361 | 28-day mortality 26.0% vs 35.0% (P = 0.062; log-rank P = 0.049) |
| TESTS 2025 | Sepsis; 22 centres in China; phase 3, double-blind, placebo-controlled; 1.6 mg every 12 hours for 7 days | 1,106 randomized (1,089 analyzed) | 28-day mortality 23.4% vs 24.1% (HR 0.97, P = 0.82); no difference |
A phase 3, double-blind, placebo-controlled hepatitis B trial found a numerically higher complete response rate with thymosin alpha 1 that did not reach statistical significance, and the authors wrote that the results “do not confirm observations of treatment efficacy reported in other clinical studies” (Mutchnick et al. 1999). FDA’s review of later work found that adding thymosin alpha 1 to peginterferon or entecavir produced similar results to those drugs alone, and concluded there was “insufficient evidence to determine the effectiveness of Ta1 for the treatment of HBV infection” (FDA 2024).
In 552 patients whose hepatitis C had not responded to peginterferon and ribavirin, adding Ta1 to re-treatment gave sustained virologic response rates of 12.7% vs 10.5% with placebo (P = 0.407), and the authors concluded it did not increase on-treatment viral response (Ciancio et al. 2012). FDA noted that the hepatitis C trials predate today’s oral direct-acting antivirals (FDA 2024).
The 2013 ETASS trial randomized 361 patients with severe sepsis at six Chinese hospitals and reported 28-day mortality of 26.0% with thymosin alpha 1 against 35.0% in controls, a difference that reached significance only in the log-rank analysis (Wu et al. 2013). That study was single-blind and had no placebo.
The same research group then ran TESTS, a much larger double-blind, placebo-controlled phase 3 trial at 22 centres in China between 2016 and 2020. Published in the BMJ in 2025, it found 28-day mortality of 23.4% with thymosin alpha 1 and 24.1% with placebo (hazard ratio 0.97, 95% CI 0.76-1.24, P = 0.82). The authors concluded the trial “found no clear evidence to suggest that thymosin α1 decreases 28 day all cause mortality in adults with sepsis” (Wu et al. 2025). Subgroup results pointed in different directions: participants under 60 had a hazard ratio of 1.67 (95% CI 1.04-2.67), while those with diabetes had a hazard ratio of 0.58 (95% CI 0.35-0.99). Adverse event rates did not differ significantly between groups.
A 2025 meta-analysis of 11 randomized trials (1,927 patients) found an overall reduction in 28-day mortality (OR 0.73), but the effect disappeared when analysis was restricted to high-quality trials (OR 0.82, P = 0.09) or multicentre trials (OR 0.86, P = 0.20). Trial sequential analysis indicated that the total sample size was still inadequate (Gu et al. 2025).
FDA’s review of melanoma, hepatocellular carcinoma and non-small cell lung cancer studies found them insufficient to demonstrate effectiveness. Most combined thymosin alpha 1 with older chemotherapy or interferon regimens, and a randomized pilot study in unresectable liver cancer found no difference in response rate or median overall survival (FDA 2024).
Across clinical studies, the most common reported adverse events were local irritation, redness and discomfort at the injection site. FDA also listed ALT flares in hepatitis B studies, thyroid-stimulating hormone abnormalities in a hepatitis C study, and fatal immune hemolytic anemia and engraftment failure in stem cell transplant recipients, and raised the possibility of graft-versus-host disease in people undergoing deliberate immunosuppression (FDA 2024).
Thymalin was developed by V. G. Morozov and V. Kh. Khavinson. They describe it as a preparation of natural thymic peptides isolated from calf thymus by mild acid extraction, from which the dipeptide Glu-Trp was later isolated and synthesized as a separate drug, thymogen (Morozov and Khavinson 1997). It has no single sequence, so it cannot be characterized the way thymosin alpha 1 can.
Developer-reported laboratory data. Morozov and Khavinson report that thymalin and thymogen both activated T-cell differentiation and T-cell recognition of peptide-MHC complexes, and altered IL-2 and interferon release by blood lymphocytes. Only the natural extract, not the synthetic dipeptides, affected the antioxidant response in thymocytes (Morozov and Khavinson 1997). These findings have not been independently replicated.
Developer-reported human data. The main human evidence is a 266-person study by its developers whose abstract does not describe randomization or blinding. Older adults were followed for 6-8 years, with thymalin, epithalamin or both given in the first 2-3 years. The authors reported 2.0-2.4-fold lower acute respiratory disease incidence and mortality 2.0-2.1 times lower in the thymalin group than in controls (Khavinson and Morozov 2003). We found no independent trial that has repeated it.
| Feature | Thymosin alpha 1 | Thymalin |
|---|---|---|
| What it is | A single defined peptide | A polypeptide extract (mixture) |
| Origin | First isolated from calf thymus fraction 5 in 1977; drug form made by chemical synthesis | Extracted from calf thymus by mild acid extraction (Morozov and Khavinson 1997) |
| Composition | 28 amino acids, N-terminal acetyl group, 3108.3 g/mol | Mixed polypeptides; the dipeptide Glu-Trp (thymogen) was isolated from it (Morozov and Khavinson 1997) |
| Natural precursor | Prothymosin alpha, cleaved by legumain | Not applicable |
| Drug names | Thymalfasin; Zadaxin | Thymalin (related synthetic drug: thymogen, Glu-Trp) |
| US status | No FDA-approved product; FDA advised against 503A bulk listing in 2024 | No FDA approval or US clinical program found |
| FDA orphan designations | Hepatocellular carcinoma (2000), DiGeorge anomaly (1998), not approved for either | None found |
| Proposed mechanism | TLR9 interactions on dendritic and lymphoid progenitor cells (FDA 2024) | T-cell differentiation and cytokine changes reported in developer studies (Morozov and Khavinson 1997) |
| Human pharmacokinetics | Serum half-life about 2 hours after subcutaneous injection | No published human data found |
| Largest human study | TESTS, 1,106 sepsis patients, double-blind; no mortality benefit | 266-person study by its developers; abstract does not describe randomization or blinding (Khavinson and Morozov 2003) |
| Who has studied it | Groups in the US (Mutchnick et al. 1999), Italy (Ciancio et al. 2012) and China (Wu et al. 2025) | Mainly the St Petersburg Institute of Bioregulation and Gerontology and collaborators (Khavinson and Morozov 2003) |
| Main weakness of the evidence | Early positive trials not confirmed by larger blinded ones | Little independent replication; product composition hard to define |
The right choice depends on what a study needs to control and what it is trying to replicate.
Whichever compound a lab chooses, identity and purity data matter. Our guide to verifying peptide purity and certificates of analysis explains what to look for.
No. FDA states it “has approved no drug products containing Ta1.” Thymalfasin holds FDA orphan designations (FDA orphan database), which are not approvals.
No. Thymosin alpha 1 is a single 28-amino-acid peptide. Thymalin is a mixture of thymus polypeptides. Both were first obtained from calf thymus, and their names are similar.
Thymalfasin is the name for chemically synthesized thymosin alpha 1, identical in sequence to the natural peptide (FDA 2024). Zadaxin is its brand name.
Not in the largest trial. TESTS, a double-blind trial of 1,106 patients published in the BMJ in 2025, found no difference in 28-day mortality between thymosin alpha 1 and placebo (Wu et al. 2025).
Peptides For Sale supplies thymosin alpha 1 for in vitro research, along with thymalin, with batch-level certificates of analysis. Check the identity and purity data for each lot before it goes into an experiment.
Research use only: Thymosin alpha 1 and thymalin sold by this store are intended strictly for in vitro and laboratory research by qualified professionals. They are not drugs, foods or dietary supplements, are not intended for human or veterinary use, and are not intended to diagnose, treat, cure or prevent any disease. This article summarizes published research for educational purposes and is not medical advice.
