Thymosin Alpha-1

Thymosin alpha-1 (thymalfasin) is a 28-amino-acid peptide originally isolated from thymus tissue and now made synthetically. It is sold under the brand name Zadaxin and is approved as a prescription drug in China and roughly three dozen other countries as an immune-modulating treatment, mainly alongside antiviral therapy for hepatitis B and C. It has never been approved by the FDA in the United States, where it remains an unapproved, investigational substance.

Research snapshot

CategoryCurrent information
Peptide categorySynthetic thymic peptide (immune modulator)
Primary research interestChronic hepatitis B/C adjunct therapy; immune support; sepsis; cancer adjunct therapy
Highest available evidencePublished human clinical trials, including a 2025 Phase 3 randomized controlled trial in sepsis (negative primary outcome)
Human research availableYes — an internationally approved regimen for hepatitis B/C, plus a large recent Phase 3 sepsis trial (n=1,106) that found no statistically significant mortality benefit
Development statusApproved as a prescription drug (Zadaxin/thymalfasin) in China and other countries; orphan drug designation reported for malignant melanoma, hepatitis B, and hepatocellular carcinoma
Regulatory statusNot FDA-approved in the United States; approved in China and a number of other countries
Last reviewedSeptember 27, 2026

Technical identity

Technical propertyInformation
Primary nameThymosin alpha-1 (thymalfasin)
Alternative namesZadaxin (brand name), TA1, Ta-1
Peptide sequenceAc-Ser-Asp-Ala-Ala-Val-Asp-Thr-Ser-Ser-Glu-Ile-Thr-Thr-Lys-Asp-Leu-Lys-Glu-Lys-Lys-Glu-Val-Val-Glu-Glu-Ala-Glu-Asn-OH (28 residues, N-acetylated)
Amino-acid length28 residues
Molecular formulaC129H215N33O55
Molecular weightNot independently re-derived for this entry from a single authoritative source
CAS Registry Number62304-98-7
PubChem CID16130571
Chemical modificationsN-terminal acetylation
Peptide classThymic peptide, immune modulator
Primary biological targetProposed TLR2/TLR9 signaling and dendritic cell maturation pathways; mechanistic claims drawn substantially from in vitro and animal pharmacology
Developer or originatorMarketed internationally as Zadaxin (thymalfasin)
Development statusApproved outside the US; recently tested in a large Phase 3 sepsis trial with a negative primary outcome

What it is

Thymosin alpha-1 is an acidic, 28-residue peptide (sequence Ac-Ser-Asp-Ala-Ala-Val-Asp-Thr-Ser-Ser-Glu-Ile-Thr-Thr-Lys-Asp-Leu-Lys-Glu-Lys-Lys-Glu-Val-Val-Glu-Glu-Ala-Glu-Asn-OH, N-acetylated at the amino terminus) that was first identified in the 1960s-70s as one of several biologically active fragments derived from prothymosin alpha, a protein present in thymus extract (thymosin fraction 5) and in most other tissues. It is not itself secreted as a free hormone in large amounts under normal physiology; most of it is now understood to be generated intracellularly from prothymosin alpha processing, and its true circulating role is still debated.

The synthetic version, thymalfasin, was developed commercially in the 1980s-90s and marketed as Zadaxin by SciClone Pharmaceuticals (later acquired by other companies as the product changed hands). It was studied and subsequently approved outside the United States as an adjunct to standard antiviral treatment for chronic hepatitis B and hepatitis C, and in some countries as an immune-response enhancer used alongside vaccines or in immunocompromised patients. Researchers have long been interested in it because it appears to act on innate and adaptive immune cells (dendritic cells, T cells, NK cells) rather than directly on a pathogen, which made it attractive as a broad immune modulator for viral infections, certain cancers as adjunct therapy, and more recently severe infections such as sepsis and COVID-19.

Thymosin alpha-1 remains commercially available as an approved drug in a number of countries but has never completed the FDA approval process in the US. It continues to be studied in registered trials, most notably a large phase 3 sepsis trial published in 2025 (see Important published research below), which is the most rigorous recent human evidence available for the peptide.

How does it work?

Plain-English explanation

Thymosin alpha-1 is thought to act like a signal that helps “tune up” the immune system rather than attacking a virus, bacteria, or tumor directly. It appears to help immune cells called dendritic cells mature and present threats to other immune cells more effectively, and to support T-cell and natural-killer-cell activity. This is why it has mainly been studied as an add-on to other treatments (antivirals, vaccines, or supportive sepsis care) rather than as a standalone therapy.

Technical explanation

Mechanistic studies describe thymosin alpha-1 acting through Toll-like receptors (particularly TLR2 and TLR9) on dendritic cells, promoting MyD88-dependent signaling that increases maturation markers and cytokine production, and modulating the balance of pro- and anti-inflammatory cytokines in ways that appear context-dependent (dampening excessive inflammation in some settings while boosting antigen-specific responses in others). It has also been reported to influence T-regulatory cell activity and to increase expression of certain MHC molecules on antigen-presenting cells. Much of this mechanistic work comes from in vitro and animal studies; the precise receptor pharmacology in humans at approved clinical doses is not fully characterized.

Potential benefits and research applications

Adjunct treatment for chronic hepatitis B and C

What is being investigated: whether adding thymosin alpha-1 to interferon or other antiviral regimens improves viral response rates in chronic hepatitis B or C. How the effect might occur: proposed enhancement of antigen-specific T-cell and innate immune responses against infected hepatocytes. Evidence: this is the indication with the most substantial published human clinical evidence, including multiple randomized trials and meta-analyses conducted mostly outside the US, which supported regulatory approval of Zadaxin in China and other countries. Strength: Tier 1 for this specific application in the countries where it is approved. Limitation: trial quality, blinding, and reporting standards vary across the older international literature, and results are less consistently replicated in populations that also receive modern direct-acting antivirals for hepatitis C, which have largely superseded interferon-based regimens.

Immune support and vaccine adjuvant use

What is being investigated: whether thymosin alpha-1 improves vaccine antibody responses or immune function in immunocompromised patients (e.g., certain cancer patients, the elderly). How the effect might occur: enhanced dendritic cell maturation and antigen presentation. Evidence: mixed and generally smaller human trials and observational studies. Strength: Tier 2, limited. Limitation: study sizes are small, endpoints vary, and effects on hard clinical outcomes (illness prevented, mortality) are not well established.

Severe infection and sepsis

What is being investigated: whether thymosin alpha-1 reduces mortality or improves immune recovery in sepsis or severe COVID-19, conditions associated with immune dysregulation. How the effect might occur: proposed restoration of impaired lymphocyte function seen in sepsis-induced immunosuppression. Evidence: the largest and most rigorous recent human evidence is the 2025 TESTS phase 3 trial in sepsis (see below), which found no significant 28-day mortality benefit. Strength: Tier 1 evidence now exists specifically for this question, and it is negative for the primary mortality endpoint. Limitation: subgroup and secondary findings from that and related trials are still being analyzed, and conclusions should not be generalized beyond the sepsis population and dosing regimen studied.

Cancer adjunct therapy

What is being investigated: use alongside chemotherapy or as supportive immune therapy in some cancers, an application with regulatory approval or off-label use in some countries. How the effect might occur: proposed general immune stimulation to counter chemotherapy-related immunosuppression. Evidence: a mix of smaller human trials and observational studies outside the US. Strength: Tier 2. Limitation: not established as a primary cancer treatment, and it is not FDA-approved for any oncology indication.

What dosage information circulates?

Figures in this section summarize amounts and schedules reported in published research or circulating online. Their inclusion documents what is reported and does not establish that a regimen is verified, safe, effective, or appropriate.

Reported use or research objectiveRoute reportedAmount reportedFrequency reportedReported durationEvidence or source category
Chronic hepatitis B/C (internationally approved Zadaxin regimen)Subcutaneous injection1.6 mgTwice weekly6 months or longer, alongside interferon-based antiviral therapyPublished human clinical trial / regulatory labeling (approving countries)
Sepsis (Phase 3 TESTS trial, negative primary outcome)Subcutaneous injectionExact schedule not independently confirmed against the full primary-text methods section; consult the primary paper directlyNot confirmed against primary textNot confirmed against primary textPublished human clinical trial (PMID 39814420, n=1,106; correction notice PMC12123687)
General wellness/longevity/”immune support” framingSubcutaneous injectionCommonly cited informally as roughly 1.5-3 mgOne to three times weeklyNot establishedCommunity / vendor reported; widely repeated but original source could not be verified

Amounts studied in human research

The internationally approved Zadaxin regimen for chronic hepatitis B/C, as documented in product labeling and clinical trial literature from approving countries, is commonly reported as 1.6 mg administered subcutaneously twice weekly, typically for 6 months or longer, used alongside interferon-based antiviral therapy (published human clinical trial / regulatory labeling, source category: journal and regulatory sources from approving countries). In the 2025 TESTS phase-3 sepsis trial (n = 1,106), thymosin alpha-1 was given by subcutaneous injection in addition to standard sepsis care; the trial publication and its correction notice are the authoritative source for the exact dosing schedule used in that study, and readers should consult the primary paper (Frontiers/BMJ, PMID 39814420) directly for the precise dose and duration rather than a secondary summary, since dosing details were not fully confirmed against the primary text during this review.

Amounts studied in animal research

Not consistently reported in the sources reviewed for this entry; older pharmacology and immunology literature describes rodent dosing in immune-response and infection models, but a single representative figure could not be confidently traced to a primary source here.

Practitioner and community-reported protocols

Outside its approved indications, thymosin alpha-1 is discussed in wellness, longevity, and peptide-community contexts using a range of self-administered subcutaneous protocols (commonly cited informally as roughly 1.5-3 mg, one to three times weekly). These figures are widely repeated across peptide-vendor and community websites, but their original source could not be verified, and they should not be treated as validated or standardized dosing (community/vendor reported).

What circulates E5

Outside its approved indications, thymosin alpha-1 is discussed in wellness, longevity, and peptide-community contexts using a range of self-administered subcutaneous protocols, commonly cited informally as roughly 1.5 to 3 mg, one to three times weekly.

These figures are widely repeated across peptide-vendor and community websites, but their original source could not be verified, and they should not be treated as validated or standardized dosing. This community-reported range is separate from, and not established as equivalent to, the internationally approved 1.6 mg twice-weekly regimen used for hepatitis B/C adjunct therapy.

Recorded as an observation about what is published elsewhere. No figure here is a dose, a protocol, or a recommendation, and nothing in this section is evidence that any amount is safe or effective.

Side effects, risks, and limitations

In its approved international indications, thymosin alpha-1 has generally been reported as well tolerated in published trials, with injection-site reactions being the most commonly reported adverse event; serious adverse events attributable to the peptide itself are reported as uncommon in the hepatitis and sepsis trial literature. However, it is an immune-modulating agent, and theoretical concerns exist around its use in people with autoimmune conditions or those on immunosuppressive therapy, since stimulating immune activity could be undesirable in those settings. Because it is not FDA-approved in the US, material sold domestically as “thymosin alpha-1” is not subject to the same manufacturing, purity, and sterility oversight as an approved pharmaceutical, and concerns about mislabeling, incorrect concentration, and contamination that apply to unregulated research peptides generally also apply here. Long-term safety data outside approved-country pharmacovigilance systems is limited.

Regulatory and developmental status

Thymosin alpha-1 (thymalfasin, brand name Zadaxin) is approved as a prescription drug in China and reported to be approved in roughly 30-plus other countries, primarily for use alongside antiviral therapy in chronic hepatitis B and C and, in some countries, as an immune-response enhancer. It has not received FDA approval in the United States and is not marketed there as an approved drug; it also appears on FDA guidance regarding bulk drug substances nominated for compounding, which reflects its unapproved status domestically rather than an endorsement. It continues to be studied in registered clinical trials, including recent sepsis research (TESTS, published 2025), and its regulatory status should be checked against current national drug registries for any specific country, since approvals and formulations can change. Status verified as of the date below based on the international regulatory and trial-registry sources cited.

Frequently asked questions

What is thymosin alpha-1?

It is a 28-amino-acid immune-modulating peptide, sold internationally as the drug Zadaxin, used mainly alongside antiviral therapy for chronic hepatitis B and C in countries where it is approved.

Is thymosin alpha-1 FDA-approved?

No. It is approved in China and a number of other countries but has not been approved by the FDA in the United States.

What dosage has been studied in clinical trials?

The most commonly reported approved regimen for hepatitis indications is 1.6 mg subcutaneously twice weekly for at least several months, alongside antiviral therapy, per international clinical trial and labeling sources.

Was thymosin alpha-1 studied for COVID-19 or sepsis?

Yes. A large phase 3 randomized trial (TESTS, published 2025 with a correction the same year) tested it in 1,106 sepsis patients and found no statistically significant reduction in 28-day mortality compared with placebo.

What dosage information circulates online outside clinical use?

Peptide-community and vendor sources commonly cite subcutaneous protocols in the range of roughly 1.5-3 mg a few times weekly, but these figures are widely repeated online without a verifiable original source and are not clinically validated.

How strong is the evidence overall?

It is strongest (Tier 1, human clinical trial evidence) for its approved hepatitis B/C adjunct indication in the countries where it is approved. Evidence for broader “immune support,” cancer adjunct use, or sepsis benefit is weaker or, in the case of the 2025 sepsis trial, specifically negative for the primary mortality endpoint.

What remains unknown?

Its precise human receptor pharmacology at approved doses, long-term safety outside monitored pharmaceutical use, and whether it provides meaningful benefit for indications beyond its approved hepatitis use remain unresolved or only partially supported by current evidence.

Bottom line

Thymosin alpha-1 is one of the few peptides in this category with genuine international drug approval and real published human clinical trial evidence, specifically as an antiviral adjunct for chronic hepatitis B and C. It is not FDA-approved in the US. Recent, methodologically strong trial evidence (the 2025 sepsis trial) did not show a mortality benefit for that use, underscoring that approval for one indication does not extend to others. Dosage figures circulating in peptide-community and wellness contexts for “immune support” are not clinically validated and are not equivalent to the approved hepatitis regimen.