Thymosin Alpha-1

Zadaxin

Grade B: Human evidence, not approved for this use

TL;DR: Thymosin alpha-1 (thymalfasin; brand name Zadaxin) is not FDA-approved in the United States for any indication, though it holds orphan drug designation for several conditions. It is approved in more than 35 countries for chronic hepatitis B and as an immune enhancer. The human evidence base is substantial but primarily generated outside the US: a Phase 3 randomized controlled trial in sepsis (the TESTS trial, n=1,106) and multiple earlier Phase 2/3 trials for hepatitis B, hepatocellular carcinoma, and COVID-19-related immunosuppression. The TESTS trial (BMJ, 2025) found no statistically significant reduction in 28-day all-cause mortality (HR 0.99, 95% CI 0.77-1.27, P=0.93). A 2025 meta-analysis of available RCTs in sepsis suggested a possible mortality reduction but rated evidence reliability as uncertain. Evidence for the range of off-label uses promoted in the US wellness market (longevity, immune optimization, post-COVID recovery) is thin and not drawn from adequately powered controlled trials. Grade B reflects that meaningful human RCT data exist but the drug is not FDA-approved and the largest sepsis trial was negative for its primary endpoint.

Key Takeaways

Grade B: Human evidence, not approved for this use
Not FDA approved: Not FDA-approved in the United States for any indication; approved in over 35 other countries for hepatitis B and immune enhancement; FDA has proposed exclusion from compounding bulk lists.
Compounding: Not FDA-approved in the United States. The FDA proposed in late 2024 not to include thymosin alpha-1 on the 503A bulk compounding list, and it is not on the 503B bulk drug substances list. Compounding pharmacies that have offered it do so without FDA authorization for the bulk substance; the regulatory status of compounded preparations is contested and subject to enforcement action.

Thymosin Alpha-1 chemical structure — Structure via PubChem CID 16130571

Mechanism

Thymosin alpha-1 is a synthetic 28-amino acid peptide derived from thymosin fraction 5 that stimulates T-lymphocyte maturation and function, enhancing cell-mediated immunity via dendritic cell and T-helper cell activation.

Evidence

Thymosin alpha-1 (thymalfasin; brand name Zadaxin) is not FDA-approved in the United States for any indication, though it holds orphan drug designation for several conditions. It is approved in more than 35 countries for chronic hepatitis B and as an immune enhancer. The human evidence base is substantial but primarily generated outside the US: a Phase 3 randomized controlled trial in sepsis (the TESTS trial, n=1,106) and multiple earlier Phase 2/3 trials for hepatitis B, hepatocellular carcinoma, and COVID-19-related immunosuppression. The TESTS trial (BMJ, 2025) found no statistically significant reduction in 28-day all-cause mortality (HR 0.99, 95% CI 0.77-1.27, P=0.93). A 2025 meta-analysis of available RCTs in sepsis suggested a possible mortality reduction but rated evidence reliability as uncertain. Evidence for the range of off-label uses promoted in the US wellness market (longevity, immune optimization, post-COVID recovery) is thin and not drawn from adequately powered controlled trials. Grade B reflects that meaningful human RCT data exist but the drug is not FDA-approved and the largest sepsis trial was negative for its primary endpoint.

Safety and risks

Human clinical trial data from international studies suggest thymosin alpha-1 is generally well-tolerated at studied doses, with injection site reactions being the most consistently reported adverse effect. However, because the drug is not FDA-approved in the US, the full safety profile has not been evaluated under FDA standards. Immune modulation carries theoretical risk in patients with autoimmune conditions, transplant recipients on immunosuppression, or patients with hematologic malignancies, as augmenting T-cell activity could exacerbate these conditions. The FDA has evaluated thymosin alpha-1 for inclusion on 503A and 503B compounding bulk substance lists and as of late 2024 proposed not to include it, citing lack of US approval and immunogenicity concerns related to peptide impurities from compounding. The FDA has issued warning letters targeting compounded thymosin alpha-1 marketed for COVID-19. Compounded preparations are not subject to FDA manufacturing quality oversight, raising purity and sterility concerns.

Interactions

Potential for additive immune effects when combined with other immunomodulators or immunosuppressants; concurrent use in transplant or autoimmune patients requires specialist oversight.

Federal compounding status

Nomination withdrawn (was Category 2) as of 2026-06-02.

This substance was nominated for the FDA 503A or 503B bulk-substances list and previously sat in the Category 2 (significant safety risk) group; the nomination was later withdrawn, so it is not on an active FDA bulks list and is not eligible for routine pharmacy compounding. FDA source

Federal status only, from public FDA records. State pharmacy-board rules vary and are not covered here. This is regulatory reporting, not legal advice. All compounds.

Compounding legality

Not FDA-approved in the United States. The FDA proposed in late 2024 not to include thymosin alpha-1 on the 503A bulk compounding list, and it is not on the 503B bulk drug substances list. Compounding pharmacies that have offered it do so without FDA authorization for the bulk substance; the regulatory status of compounded preparations is contested and subject to enforcement action.

Sources

Thymosin Alpha-1 is Not FDA approved. PeptideGrids presents evidence and regulatory status for informational purposes only. We do not sell, supply, source, or help anyone obtain this compound, and we provide no dosing or administration guidance. This is not medical advice; consult a licensed clinician. Full disclaimer.

Last reviewed June 1, 2026 by PeptideGrids editorial team (independently audited).