What it is
Thymosin alpha-1 is a chain of 28 amino acids that the body makes naturally. It was first purified in the 1970s from calf thymus, the organ where T cells (a type of white blood cell) mature. The version in medicines and research today is made synthetically, and its generic drug name is thymalfasin.
It has been studied as an immune modulator in chronic viral infections, severe infections such as sepsis, and alongside vaccines or cancer treatment. A brand called Zadaxin is approved in China, Italy and a number of other countries. It is not approved by the FDA in the United States.
Thymalfasin is Ac-SDAAVDTSSEITTKDLKEKKEVVEEAEN-OH (C129H215N33O55, 3108.3 g/mol, CAS 62304-98-7), a highly acidic, N-terminally acetylated peptide identical to the N-terminal segment of prothymosin α (residues 2–29 of the precursor, after removal of the initiator methionine; UniProt P06454). Goldstein et al. (1977) sequenced it from thymosin fraction 5, a partially purified calf-thymus extract.
Its immunomodulatory activity is attributed at least partly to Toll-like receptor 9 signalling on dendritic cells and lymphoid progenitors (FDA, 2024). In rodent models it has been reported to suppress tumour growth and viral infection, to reduce sepsis and to raise antibody titres to some vaccines, usually at fixed doses whose human equivalents are well above the doses used clinically; dose-response relationships have not been established.
Pharmacokinetics: after 900 µg/m² subcutaneously in nine healthy volunteers, tmax was 1–2 hours, elimination half-life under 3 hours and apparent volume of distribution 30–40 L, with no accumulation over 5 days of daily dosing (Rost et al. 1999). In rats given it intravenously, the half-life was about 2–3 minutes. Trial regimens have ranged from 1.6 mg subcutaneously twice weekly (hepatitis B) to 1.6 mg every 12 hours (sepsis).
Who made it and when
Allan Goldstein and colleagues isolated and sequenced thymosin alpha-1 from calf thymus in 1977, as one of several active pieces in a thymus extract they had been studying. Chemical synthesis followed, and a US company, Alpha 1 Biomedicals, ran a hepatitis B trial in the United States that did not reach statistical significance. SciClone Pharmaceuticals then acquired rights, named the product Zadaxin, and won approvals abroad, mainly in Asia, the Middle East and Latin America, with most sales in China. Its later US trials in hepatitis C did not succeed, and no US approval followed.
Goldstein et al. (1977) reported the 28-residue sequence and proposed the thymosin nomenclature. According to SciClone’s 2004 annual report (Form 10-K), Alpha 1 Biomedicals completed a 99-patient US phase 3 trial in chronic hepatitis B in 1994; 25% on thymosin α1 versus 13% on placebo reached the endpoints, which was not statistically significant, and the data were never submitted to FDA. Mutchnick et al. (1999, n=97) report the same 25% versus 13% for sustained loss of HBV DNA with HBeAg negativity. SciClone stated that Zadaxin was approved in over 30 countries, “primarily in Asia, the Middle East and Latin America”, principally for hepatitis B, with some approvals for hepatitis C, as a vaccine adjuvant or as a chemotherapy adjuvant, and that 91% of 2004 sales were in China; Sigma-Tau held marketing rights in most of Western Europe. FDA (2024) notes it is not approved in the US, Japan or Europe except Italy, and that it could not verify every claimed approval. Two US phase 3 trials of Zadaxin with peginterferon in hepatitis C were reported by the company in 2005–2006 as not meeting their primary endpoints.
FDA’s orphan database lists a designation for hepatocellular carcinoma (SciClone, 2000-03-06), never approved for that use.
What the data say
There are many human studies, most of them from China and many small or unblinded. In chronic hepatitis B, results were mixed: a randomised trial in Taiwan without a placebo reported more patients clearing the virus, while a placebo-controlled US trial did not reach significance. In sepsis, an early open-label Chinese trial reported fewer deaths, but a much larger double-blind trial of 1,106 patients, published in 2025, found no difference in 28-day survival. During COVID-19, a small look-back study from Wuhan reported fewer deaths, but later pooled analyses mostly did not. The FDA reviewed the evidence in 2024 and found it insufficient for any of the 12 uses it examined.
Hepatitis B: Chien et al. (1998, Taiwan, n=98) reported complete virological response at 18 months in 40.6% after a 26-week course of 1.6 mg twice weekly versus 9.4% in untreated controls (P=.004), without placebo or blinding. The US multicentre, double-blind trial (Mutchnick et al. 1999, n=97) found 14% versus 4% complete response (P=0.084); the authors wrote that the results “do not confirm” earlier efficacy reports.
Sepsis: ETASS (Wu et al. 2013, n=361, single-blind) reported 28-day mortality of 26% versus 35%. The confirmatory TESTS trial (NCT02867267, n=1,106, double-blind, 1.6 mg every 12 hours for up to 7 days) found 23.4% versus 24.1% (HR 0.99, 95% CI 0.77–1.27); a prespecified subgroup analysis suggested a possible differential effect by age, with an HR of 1.67 in patients under 60 and 0.81 in those 60 or older. The trial was partly funded by SciClone.
COVID-19: Liu et al. (2020, retrospective, n=76 severe cases) reported mortality of 11.1% versus 30.0%; of four meta-analyses FDA reviewed, three found no mortality reduction. FDA’s 2024 review concluded there was a lack of evidence supporting subcutaneous thymosin α1 for any evaluated use.
Regulatory picture
Approval: no thymosin alpha-1 product is approved by the FDA. Approvals in China, Italy and elsewhere do not apply in the United States. The FDA has granted an orphan-drug designation, an incentive for development in rare diseases, for liver cancer; that is not an approval. Compounding: in 2023 the FDA put it in “Category 2”, the group of substances pharmacies should not compound from. In 2024 it was taken off that list after its nominator withdrew, but the FDA reviewed it anyway, and in December 2024 an FDA advisory committee voted 17 to 4 against allowing pharmacies to compound it. It is not on the list of allowed ingredients. Enforcement: FDA warning letters have covered online “Thymosin Alpha 1” sold with COVID-19 claims (2020) and compounded thymosin alpha (2021).
Approval: none in the US; no BLA or NDA approval exists. FDA’s orphan database shows a designation for hepatocellular carcinoma (2000). SciClone announced in March 2006 that thymalfasin had also been granted orphan designation for stage IIb–IV malignant melanoma; that record could not be retrieved from FDA’s database for this article, and other designations cited online were not verified.
Compounding: “Thymosin-Alpha 1 (Ta1)” was listed in 503A Category 2 in FDA’s update of 2023-09-29. The update of 2024-09-27 removed it because “the nomination was withdrawn by the nominator”, while announcing that FDA would consult the Pharmacy Compounding Advisory Committee anyway. On 2024-12-04, with FDA proposing exclusion for uses including hepatitis B and C, HIV, COVID-19, vaccine response, melanoma, hepatocellular carcinoma, NSCLC, sepsis, post-transplant infection, COPD and ME/CFS, the committee voted 4 yes and 17 no for both the free base and the acetate. FDA’s safety-risk page (2026-04-22) still lists Ta1’s immunogenicity concerns among withdrawn substances. Ta1 was not on the July 2026 agenda, and no proposed or final rule on it was found in the Federal Register. It is not on the 503A bulks list, so this article records compounding status as unknown.
