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Thymosin Alpha-1

Tier 1 · Human trials
Also known as Thymalfasin · Zadaxin · Thymosin alpha 1

The strongest evidence present is Tier 1: multiple human randomized controlled trials (a multicentre double-blinded phase 3 sepsis trial, the ETASS and TESTS sepsis trials, hepatitis B/C RCTs, a COVID-19 RCT, and an H1N1 influenza-vaccine RCT in hemodialysis patients) plus a meta-analysis of 11 RCTs. Many mechanism and tumor-microenvironment claims rest on expert opinion, in vitro, or animal data, and several key efficacy signals are contested — the sepsis mortality benefit weakens in high-quality analyses and the COVID-19 recovery findings did not reach significance.

Half-life
~2 h
Routes
Subcutaneous injection
Goals
Immune support and modulation · Antiviral / infectious disease support · Sepsis / critical care immunomodulation · Cancer immune adjunct · Vaccine adjuvant · Healthy aging / immunosenescence
Cost / mg
Not recorded

How it works

Thymosin alpha-1 is a 28-amino-acid peptide the thymus gland naturally makes; reviews describe it as long recognized for modifying, enhancing and restoring immune function. Sources report it helps train and coordinate immune cells — encouraging T cells to mature and specialize, activating natural killer cells and dendritic cells, and tuning the mix of signaling molecules (cytokines) the immune system releases. One web source attributes to it a dual capacity to both boost an underactive immune response and calm an overactive, inflammatory one. Much of this mechanistic picture comes from expert opinion, in vitro work and animal studies rather than human trials.

Overview

Overview

Thymosin alpha-1 (also called thymalfasin; brand name Zadaxin) is a 28-amino-acid peptide. A tier 1 review reports it is naturally occurring in the thymus and has long been recognized for modifying, enhancing and restoring immune function. A web source reports it was first isolated from thymic tissue in 1977 by Allan Goldstein and colleagues at the George Washington University School of Medicine, and an expert consensus notes it was initially isolated from calf thymus and is also expressed in humans with an identical sequence. A regulatory document lists a molecular weight of 3108.28 g/mol and a 28-residue acetylated sequence. A structural review describes it as a short, highly charged, intrinsically unstructured protein under natural conditions.

Reported Uses

Reviews report Tα1 has been utilized in immunocompromised states and malignancies, as an enhancer of vaccine response, and as a means of curbing morbidity and mortality in sepsis and numerous infections. A review describes it as an immunostimulatory peptide commonly used as an immune enhancer in viral infectious diseases such as hepatitis B, hepatitis C and AIDS. A tier 3 web source describes it as a research peptide of interest in hepatology, oncology, immunology and neurology, and notes it first attracted interest as a possible immune enhancer and vaccine adjuvant. A tier 3 web source claims it might help with autoimmune diseases, chronic viral hepatitis and systemic inflammation and may promote better outcomes in cancer, Lyme disease, sepsis and allergies through immune modulation, though these named-disease benefits are not established by clinical trials.

Regulatory Status

Sources agree the synthetic version thymalfasin (Zadaxin) is approved in more than 35 countries for chronic hepatitis B, chronic hepatitis C, and as an immune adjunct in cancer care, but that it is not FDA-approved in the United States and is being reviewed for inclusion on the 503A bulk drug substances list.

Clinical Evidence

Sepsis. A multicentre, double-blinded, randomised, placebo-controlled phase 3 trial (the TESTS trial, described below) set out to test whether Tα1 is efficacious and safe for sepsis, and the ETASS study evaluated it for severe sepsis in a multicenter, single-blind, randomized controlled trial across critical care departments in China. A meta-analysis of 11 RCTs (967 Tα1 patients vs 960 controls) demonstrated a significant reduction in 28-day mortality (OR 0.73, 95% CI 0.59–0.90, P = 0.003). However, the same review reports that analyses restricted to high-quality RCTs showed no significant mortality benefit (OR 0.82, 95% CI 0.65–1.03, P = 0.09) and a multi-center subgroup analysis also showed no benefit (OR 0.86, 95% CI 0.68–1.08, P = 0.20), with 75% of patients coming from two large RCTs. The TESTS trial (1106 patients) found no mortality reduction or clinical improvement, though elderly and diabetic subgroups showed potential effects, and trial sequential analysis suggested the current sample size is inadequate. A heterogeneity-of-treatment-effects analysis reported potential benefits in the cancer subgroup (moderate credibility) and in diabetes and coronary heart disease subgroups (low credibility). Another review describes Tα1 as an immune modulator that reduced sepsis mortality, improved HLA-DR expression on monocytes and diminished secondary infection, while cautioning that sepsis is a heterogeneous syndrome and that present studies are not focused on immunosuppressive individuals.

Hepatitis B and C. A review reports HBV DNA clearance at six months in 9 of 17 patients receiving TA1 versus 10 of 16 on interferon alfa-2b and 4 of 15 historical controls; an open-label trial found HBV DNA clearance in 53% of patients at six months, and an RCT found clearance in 40.6% treated for 6 months and 25.6% for 12 months versus 9.4% of untreated controls. For hepatitis C, one trial found no significant difference in ALT normalization between TA1 and placebo, while another found normal ALT at six months in 71% of combination TA1 + IFN-alpha 2b patients versus 35% on IFN alone, and HCV RNA clearance in 65% versus 29%. A web source notes that interferon-combination trials have not provided definitive evidence of efficacy.

Vaccine adjuvant / immunosenescence. A randomized trial reported that Tα1 (3.2 mg and 6.4 mg doses) combined with an adjuvanted pandemic H1N1v influenza vaccine enhanced immunogenicity in hemodialyzed patients. Reviews report Tα1 can improve vaccine response in the elderly and mitigate immunosenescence.

COVID-19. A randomized trial of 49 patients reported Tα1 may be a treatment option, with a higher incidence of clinical recovery in low-flow (sHR 1.48, 95% CI .68–3.25) and high-flow (1.28, 95% CI .35–4.63) oxygen subgroups — neither significant — while patients with baseline low-flow oxygen had 3.84 times more CD4+ T cells on day 5 than controls (P = .01).

Cancer. An animal study reports Tα1 reprograms M2-like tumor-associated macrophages toward an antitumoral phenotype and enhances the antitumor efficacy of adenovirus via CD8 T cells; a review describes a hybrid drug fusing TNFα and Tα1 with antitumor activity and reduced toxicity.

A regulatory document states Tα1 has been used to support immunity in over 3,000 patients and in over 70 clinical studies.

What the research shows

221 findings extracted from the 29 sources cited below, strongest evidence first within each group. Every one links to the source it came from.

What human studies found

Based on 25 human trial findings, 9 human study findings, 1 animal finding, 10 expert opinion findings and 1 theoretical finding.

  • human trialThymosin α1 is efficacious and safe for sepsis2

  • human trialThymosin alpha 1 was evaluated for efficacy in severe sepsis in a multicenter, single-blind, randomized and controlled trial3

  • human trialThe study (ETASS) was a multicenter trial conducted across multiple departments of critical care medicine in China3

  • human trialMeta-analysis of 11 RCTs demonstrated significant reduction in 28-day mortality associated with Tα1 administration (OR 0.73, 95%CI: 0.59-0.90, P = 0.003)7

  • human trialAnalyses of high-quality RCTs did not reveal a mortality benefit (OR 0.82, 95%CI: 0.65-1.03, P = 0.09)7

  • human trialMulti-center subgroup analysis did not reveal a mortality benefit (OR 0.86, 95%CI: 0.68-1.08, P = 0.20)7

  • human trialHeterogeneity of treatment effects analysis showed potential benefits in cancer subgroup (moderate credibility)7

  • human trialPotential benefits noted in diabetes subgroup (low credibility)7

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  • human trialPotential benefits noted in coronary heart disease subgroup (low credibility)7

  • human trialTrial sequential analysis suggests current sample size is inadequate7

  • human trialTESTS trial with 1106 patients found no mortality reduction or clinical improvement with Tα1, though elderly and diabetic subgroups showed potential effects7

  • human trialIncidence of clinical recovery was higher for treated patients with baseline low-flow oxygen (subdistribution hazard ratio, 1.48 [95% confidence interval, .68-3.25]), although the difference was not significant8

  • human trialIncidence of clinical recovery was higher for treated patients with baseline high-flow oxygen (1.28 [.35-4.63]), although the difference was not significant8

  • human trialAmong patients with baseline low-flow oxygen, treated patients had an average difference of 3.84 times more CD4+ T cells on day 5 than on day 1 compared with control patients8

  • human trialThymosin alpha 1 enhanced the immunogenicity of the pandemic influenza vaccine in hemodialyzed patients14

  • human trialThymosin alpha 1 combined with adjuvated pandemic H1N1v influenza vaccine resulted in better Geometric Mean Titer (GMT) and Geometric Mean Ratio (GMR) of HI on Day 21 compared to vaccine alone14

  • human trialA large proportion of patients in Vaccine+Thymosin alpha 1 groups achieved seroconversion by Day 2114

  • human trialCHMP criteria were fully met in groups treated with Vaccine+Thymosin alpha 114

  • human trialHBV DNA clearance at six months in 9 of 17 patients receiving TA1, compared with 10 of 16 patients treated with interferon alfa-2b and 4 of 15 historical controls16

  • human trialRandomized, controlled trial found HBV DNA clearance in 40.6% of patients treated with TA1 for 6 months compared with 9.4% of untreated controls16

  • human trialRandomized, controlled trial found HBV DNA clearance in 25.6% of patients treated with TA1 for 12 months compared with 9.4% of untreated controls16

  • human trialIn one hepatitis C trial, the number of patients who achieved normal serum alanine aminotransferase (ALT) levels did not differ significantly between TA1 and placebo16

  • human trialOne trial found a normal serum ALT level at six months in 71% of patients receiving combination TA1 and IFN-alpha 2b, versus 35% of patients receiving IFN-alpha 2b alone16

  • human trialHepatitis C virus RNA clearance occurred in 65% of patients treated with combination TA1 and IFN-alpha 2b and 29% of patients treated with IFN-alpha 2b alone16

  • human trialTrial comparing combination TA1 and IFN-alpha 2b with IFN-alpha 2b alone and with placebo found normalization of ALT levels at six months in 37.1% of patients receiving combination therapy, 16.2% of patients receiving IFN-alpha 2b alone, and 2.7% of patients receiving placebo16

  • human studySingle or combined treatment with Tα1 reduced the mortality rate of sepsis11

  • human studyTα1 treatment improved the expression of HLA-DR on monocyte11

  • human studyTα1 treatment diminished the incidence of secondary infection11

  • human studyTα-1 monotherapy is effective in suppressing viral replication compared with untreated control or conventional interferon13

  • human studyCombination therapy of Tα-1 plus either lamivudine or IFN-α showed better effects on HBV DNA suppression and HBeAg seroconversion13

  • human studySeveral studies showed that Thymosin alpha-1 ameliorates the performance of influenza vaccination in elderly and subjects at risk15

  • human studyOpen-label trial found HBV DNA clearance in 53% of patients at six months16

  • human studyPreclinical and clinical studies show that Tα1 can improve vaccine response in the elderly and mitigate immunosenescence.19

  • human studyEfforts have been made to treat immune deficiency in aged and cancer-bearing humans with thymosin alpha 122

  • animalExogenously supplied and adenovirus-produced Tα1 orchestrate TAM reprogramming and enhance the antitumor efficacy of ADV via CD8 T cells20

  • expert opinionClinical evidence has been accumulated for application of thymosin alpha 1 in infectious diseases and critical care medicine1

  • expert opinionThymosin alpha 1 has long been recognized for modifying, enhancing, and restoring immune function5

  • expert opinionStudies have postulated that thymosin alpha 1 could help improve the outcome in severely ill coronavirus disease 2019 patients by repairing damage caused by overactivation of lymphocytic immunity5

  • expert opinionExtensive studies in both the preclinical and clinical setting have demonstrated improvements in immune system cell subsets and the potential of Ta1 for the treatment of a range of diseases12

  • expert opinionThymosin alpha 1 has been used to support immunity in over 3,000 patients and in over 70 clinical studies17

  • expert opinionObservable immune benefits often emerging within 2–4 weeks of consistent use25

  • expert opinionAugmented vaccine responses25

  • expert opinionTa1 has received regulatory approval in some countries for certain indications such as viral infections, cancer, and chronic hepatitis B and C26

  • expert opinionTa1 has shown potential as an immunomodulatory peptide in improving treatment outcomes for hepatitis C virus (HCV) when used in combination with standard care26

  • expert opinionClinical trials combining Ta1 with interferon-based therapies have not provided definitive evidence supporting its efficacy26

  • theoreticalThymosin alpha 1 could help improve the outcome in severely ill coronavirus disease 2019 patients by repairing damage caused by overactivation of lymphocytic immunity10

How it works

Based on 1 human trial finding, 1 human study finding, 7 animal findings, 8 in vitro findings, 69 expert opinion findings and 7 theoretical findings.

  • human trialTα1 increases CD4+ T-cell count among patients with baseline low-flow oxygen support faster than the standard of care8

  • human studyThymosin α-1 (Tα-1), as an immunomodulatory agent, can enhance T-cell response in CHB patients13

  • animalThymosin α1 reverses T cell exhaustion7

  • animalThymosin α1 enhances Th1-dependent antifungal immunity7

  • animalThymosin alpha 1 (Ta1) is a peptide originally isolated from thymic tissue as the compound responsible for restoring immune function to thymectomized mice12

  • animalType V adenovirus (ADV) induces the polarization of tumor-associated macrophages (TAMs) to the M2 phenotype20

  • animalType V adenovirus increases the infiltration of regulatory T cells (Tregs) in the tumor microenvironment (TME)20

  • animalThymosin alpha 1 (Tα1) reprograms M2-like TAMs toward an antitumoral phenotype20

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  • animalThymosin alpha 1 reprograms the tumor microenvironment into a state more beneficial for antitumor immunity20

  • in vitroThymosin α1 promotes naive T cell maturation7

  • in vitroThymosin α1 alleviates cytokine storms7

  • in vitroThymosin alpha-1 is a short, highly charged, intrinsically unstructured protein under natural conditions21

  • in vitroStructure can be induced in thymosin alpha-1 by charge neutralization at low pH21

  • in vitroStructure can be induced in thymosin alpha-1 by addition of Zn(2+) ions21

  • in vitroStructure can be induced in thymosin alpha-1 by organic reagents such as trifluoroethanol, hexafluoropropanol, or n-dodecyltrimethylammonium bromide21

  • in vitroStructure can be induced in thymosin alpha-1 by interactions with natural binding partner proteins21

  • in vitroThymosin alpha-1 structures have been studied by circular dichroism, nuclear magnetic resonance, and crystallographic methods21

  • expert opinionThymosin alpha 1 (Tα1), initially isolated from calf thymus, is also expressed in humans with an identical sequence1

  • expert opinionTα1 has multiple immune activities, such as enhancing antiviral, antibacterial and antitumor activities in humans1

  • expert opinionTα1 may directly or indirectly affect the quantity and function of various immune cells, helping prevent invasion by external pathogens including bacteria and viruses, and eliminate internal toxic products such as tumor cells1

  • expert opinionTα1 has been proven to be an agonist of TLR-2 and TLR-9, activating TLRs on myeloid and plasmacytoid dendritic cells1

  • expert opinionTα1 promotes the transformation of Th lymphocytes into Th1 subtype, causing increase in Th1-type cytokines such as IL-2 and interferon IFN-γ and CD8+ T lymphocyte counts1

  • expert opinionTα1 may enhance innate immunity and increase the activity of NK cells and macrophages1

  • expert opinionTα1 may increase the activity of indoleamine-2,3-dioxygenase in plasmacytoid dendritic cells, leading to increase in FoxP3+ regulatory T lymphocytes1

  • expert opinionThymosin alpha 1 is a peptide naturally occurring in the thymus that has long been recognized for modifying, enhancing, and restoring immune function4

  • expert opinionThymosin alpha 1 has known biochemical properties including antibacterial and antiviral properties4

  • expert opinionThymosin alpha 1 is a peptide naturally occurring in the thymus5

  • expert opinionThymosin alpha 1 could prevent the excessive activation of T cells5

  • expert opinionThymosin alpha 1 has known antibacterial and antiviral properties5

  • expert opinionThymosin Alpha-1 (TA1) is a 28-amino-acid peptide your thymus gland naturally makes6

  • expert opinionIt helps train and coordinate the immune cells that fight viruses and other infections6

  • expert opinionThymosin alpha 1 is a peptide naturally occurring in the thymus10

  • expert opinionThymosin alpha 1 has long been recognized for modifying, enhancing, and restoring immune function10

  • expert opinionThymosin alpha 1 has antibacterial and antiviral properties10

  • expert opinionThymosin alpha 1 acts as an immune modulator, exerting biological influence in activating and restoring dysregulated immune response for patients with sepsis11

  • expert opinionTa1 has a pleiotropic mechanism of action, affecting multiple immune cell subsets that are involved in immune suppression12

  • expert opinionTa1 acts through Toll-like receptors in both myeloid and plasmacytoid dendritic cells, leading to activation and stimulation of signaling pathways and initiation of production of immune-related cytokines12

  • expert opinionThymosin alpha-1 is a biologically active peptide made up of 28 amino acids15

  • expert opinionThymosin alpha-1 can enhance T-cells, dendritic cell and antibody responses15

  • expert opinionThymosin alpha-1 can modulate cytokines and chemokines production15

  • expert opinionTA1 is thought to modulate the immune system by augmenting T-cell function16

  • expert opinionTA1 may affect thymocytes by stimulating their differentiation or by converting them to active T cells16

  • expert opinionModulates innate immunity (pleiotropic)17

  • expert opinionImproves Th1 immune responses and helps balance Th1/Th217

  • expert opinionPromotes T cell (Tregs) differentiation and maturation17

  • expert opinionDecreases T-cell apoptosis17

  • expert opinionImproves CD3+, CD4+ and CD8+17

  • expert opinionImproves production of IL-1 beta, IFN-γ, IL-2, IL-3, IL-6, IL-1017

  • expert opinionImproves NK cell activity and TNF-alpha17

  • expert opinionImproves macrophages and B cells17

  • expert opinionUp regulates MHC Class I expression in antigen expressing cell17

  • expert opinionTumor specific antigens; anti-tumor properties17

  • expert opinionInhibits viral replication17

  • expert opinionActivates indoleamine 2,3-dioxygenase enzyme - dampens immunity17

  • expert opinionImproves dendritic cell tryptophan catabolism17

  • expert opinionAntioxidant properties – improves intracellular glutathione17

  • expert opinionDown-regulates the activity of terminal deoxynucleotide transferase (TdT) in TdT1 thymocytes, suggesting a role for Ta1 in thymocyte maturation17

  • expert opinionAntagonizes both activation induced (anti-CD3) and glucocorticoid-induced thymocyte apoptosis17

  • expert opinionStimulates activity of Indoleamine-2,3-Dioxygenase (IDO), leading to an increase in FoxP3 IL-10 producing regulatory T cells17

  • expert opinionTα1 can influence the functions of immune cells, such as T cells, B cells, macrophages, and natural killer cells, by interacting with various Toll-like receptors (TLRs)18

  • expert opinionTα1 can bind to TLR3/4/9 and activate downstream IRF3 and NF-κB signal pathways, thus promoting the proliferation and activation of target immune cells18

  • expert opinionTLR2 and TLR7 are associated with Tα1. TLR2/NF-κB, TLR2/p38MAPK, or TLR7/MyD88 signaling pathways are activated by Tα1 to promote the production of various cytokines18

  • expert opinionTα1 enhances the innate and adaptive immune responses18

  • expert opinionThymosin alpha 1 is a putative thymic hormone produced by the thymus24

  • expert opinionThymosin alpha 1 circulates and acts on both prothymocytes and mature T-cells in the periphery24

  • expert opinionThymosin alpha 1 maintains T-cell commitment to the T-cell system and its functions24

  • expert opinionIt may work by helping immune cells like T cells and natural killer cells do their jobs better25

  • expert opinionThymosin Alpha 1 is a naturally occurring 28-amino acid peptide derived from the thymus gland25

  • expert opinionEnhanced T-cell maturation and function25

  • expert opinionImproved dendritic cell activity25

  • expert opinionIncreased natural killer cell cytotoxicity25

  • expert opinionThymosin Alpha 1 has a dual capacity to both stimulate underactive immune responses and modulate overactive inflammatory states25

  • expert opinionIt demonstrates remarkable homeostatic properties, enhancing immune surveillance while simultaneously promoting tolerance mechanisms that prevent autoimmune reactions25

  • expert opinionThymosin Alpha 1 exerts significant immunomodulatory effects through its interaction with Toll-like receptors (TLRs), particularly TLR2, TLR7, and TLR9 on dendritic cells and other antigen-presenting cells25

  • expert opinionThis activation triggers intracellular signaling cascades involving MyD88 and NF-kB pathways, resulting in enhanced cytokine production and improved antigen presentation25

  • expert opinionTa1 upregulates the expression of terminal deoxynucleotidyl transferase (TdT) and CD4/CD8 surface markers, facilitating proper T-cell receptor rearrangement and selection processes25

  • expert opinionIt enhances interferon-alpha (IFN-a), interferon-gamma (IFN-y), and interleukin-2 (IL-2) production while simultaneously suppressing pro-inflammatory cytokines such as IL-1B and TNF-a in contexts of excessive inflammation25

  • expert opinionTa1 demonstrates antioxidant properties through upregulation of superoxide dismutase (SOD) and glutathione peroxidase activity25

  • expert opinionThymosin alpha-1 (Ta1) is derived from the thymus gland and enhances immune responses mediated by T-cells through various mechanisms including promoting T-cell differentiation and maturation, activating natural killer cells, stimulating dendritic cells, and triggering the release of proinflammatory cytokines26

  • expert opinionTa1 acts as an immunoregulatory molecule, modulating immune responses and promoting immune system functionality26

  • expert opinionTa1 modulates immune responses by influencing the functions of different immune cells while regulating cytokine and chemokine production26

  • expert opinionThymosin alpha-1 improves T-cell differentiation and antigen recognition and activation, thereby enhancing the immune response against pathogens including viruses and cancer cells26

  • expert opinionTa1 demonstrates direct antiviral effects against various viruses, including hepatitis B and C, HIV, and CMV26

  • expert opinionTa1 has been shown to enhance the activity of natural killer (NK) cells and boosts NK cell-mediated cytotoxicity26

  • expert opinionTa1 promotes the production and activation of cytotoxic T-cells, NK cells, and dendritic cells involved in tumor surveillance and elimination26

  • expert opinionThymosin alpha 1 is a thymomimetic peptide that may augment TH-1 and DTH (delayed type hypersensitivity) responses28

  • theoreticalThymosin alpha 1 could help improve the outcome in severely ill coronavirus disease 2019 patients by repairing damage caused by overactivation of lymphocytic immunity4

  • theoreticalThymosin alpha 1 could prevent the excessive activation of T cells4

  • theoreticalThymosin alpha 1 could prevent the excessive activation of T cells10

  • theoreticalThymosin alpha-1 (Tα1), a peptide hormone produced by the thymus, exhibits potent immunomodulatory, anti-inflammatory, and antioxidant properties.19

  • theoreticalIt helps restore immune function by stimulating T-cell differentiation, enhancing thymic output, and modulating dendritic cell and macrophage activity.19

  • theoreticalThe hybrid drug (a fusion of tumor necrosis factor alpha (TNFα) and Tα1) combines Tα1's immunomodulation with TNF's antitumor activity but has reduced toxicity.19

  • theoreticalThymosin alpha 1 is involved in paracrine and autocrine mediator interactions among thymic stromal cells and developing thymocytes required for thymic function at the local level22

Dosing

Based on 7 human trial findings and 9 expert opinion findings.

  • human trialThe standard clinical schedule, validated in chronic hepatitis B trials, is 1.6 mg twice weekly for 6 to 12 months6

  • human trialAlmost every published TA1 dose traces back to one core protocol: 1.6 mg subcutaneously twice weekly across the chronic hepatitis B and C trials6

  • human trialFor adults weighing under 40 kg (88 lb), the labeled adjustment is 40 mcg/kg twice weekly, subcutaneous6

  • human trialChronic hepatitis B monotherapy duration is 6 months from Zadaxin pooled analysis of 3 RCTs6

  • human trialChronic hepatitis C with interferon duration is 6-12 months from Zadaxin pooled analysis (2 RCTs + 1 historical control)6

  • human trialSevere sepsis (TESTS, BMJ 2025) used 7 days continuous (every 12 hours) in a Phase 3 RCT across 22 Chinese centers6

  • human trialFor hepatitis B and C, TA1 should be administered subcutaneously twice a week16

  • expert opinionTA1 is given by subcutaneous injection6

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  • expert opinionFrom a 10 mg vial reconstituted with 2 mL bacteriostatic water (5 mg/mL), 1.6 mg = 0.32 mL = 32 units on a U-100 insulin syringe6

  • expert opinionSubQ General Dosage: 3mg/ml 5ml vial, 1.6 mg SubQ, 2 times weekly for 6-12 months17

  • expert opinionPatients weighing < 40 kg, dosage adjusted to 40 mcg/kg, 2 times weekly17

  • expert opinionTreatment from 2 weeks for viral infection and 3 months or longer for HIV/cancer/Hepatitis B, C or complicated immune suppression or over-activation17

  • expert opinionStandard dosing ranges from 1.6 mg to 6.4 mg subcutaneously two to three times weekly25

  • expert opinion1.6 mg subcutaneously twice weekly is the most common starting dose for general immune support and has demonstrated efficacy in clinical settings with minimal adverse effects25

  • expert opinion1.6 mg daily or 3.2 mg twice weekly for initial treatment phases, potentially extending to 6.4 mg twice weekly in severe cases under medical supervision25

  • expert opinionClinical trials in hepatitis B used 1.6 mg twice weekly for 6–12 months25

How the body handles it

Based on 3 human study findings.

  • human studyTA1 is rapidly absorbed, achieving peak serum concentrations within two hours16

  • human studyBlood levels return to baseline within 24 hours16

  • human studyThe serum half-life is approximately 2 hours16

Safety and side effects

Based on 6 human trial findings and 16 expert opinion findings.

  • human trialNine serious adverse events among treated patients were deemed not related to Tα18

  • human trialNo adverse events were found to be related to Thymosin alpha 1 or the Focetria vaccine14

  • human trialThymosin alpha 1 did not affect hematology or blood-chemistry values14

  • human trialThymosin alpha 1 proved safe and well tolerated14

  • human trialTA1 is well tolerated16

  • human trialMost studies observed only local irritation at the injection site16

  • expert opinionIt is not FDA-approved in the United States and is currently being reviewed for inclusion on the 503A bulk drug substances list6

  • expert opinionThymosin alpha 1 peptide is reported safe in recommended dosages17

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  • expert opinionSince 1979, thymosin alpha-1 is well tolerated with a very favorable toxicity profile in more than 3,000 individuals treated to date17

  • expert opinionThymosin alpha 1 has been reported to be well tolerated even in patients with decompensated liver disease, renal disease requiring hemodialysis and primary immunodeficient individuals17

  • expert opinionAs with all injections, redness and pain at the site of injection may be present17

  • expert opinionRare adverse reactions include erythema, transient muscle atrophy, polyarthralgia combined with hand edema, and rash17

  • expert opinionA transient increase in ALT to more than twice baseline value can occur during thymosin alpha 1 therapy17

  • expert opinionUse caution if administering to pregnant or nursing women17

  • expert opinionDo not use in individuals being deliberately immunosuppressed17

  • expert opinionSafety in pediatrics has not been established17

  • expert opinionIt remains unapproved by the U.S. FDA25

  • expert opinionThymosin Alpha 1 does not appear to induce receptor downregulation or tachyphylaxis with extended use25

  • expert opinionInjection site reactions are a risk associated with thymosin alpha-126

  • expert opinionHeadache is a risk associated with thymosin alpha-126

  • expert opinionNausea and vomiting are risks associated with thymosin alpha-126

  • expert opinionFatigue is a risk associated with thymosin alpha-126

What people use it for

Based on 3 human trial findings, 7 human study findings, 2 animal findings and 24 expert opinion findings.

  • human trialStudy design: multicentre, double blinded, randomised, placebo controlled, phase 3 trial2

  • human trialThymosin α1 shows promise as an immunomodulator for sepsis7

  • human trialThymosin-α-1 (Tα1) may be a treatment option for coronavirus disease 2019 (COVID-19)8

  • human studyThymosin alpha 1 has been utilized in the treatment of immunocompromised states and malignancies4

  • human studyThymosin alpha 1 has been utilized as an enhancer of vaccine response4

  • human studyThymosin alpha 1 has been utilized as a means of curbing morbidity and mortality in sepsis and numerous infections4

  • human studyThymosin alpha 1 has been utilized in the treatment of immunocompromised states and malignancies10

  • human studyThymosin alpha 1 used as an enhancer of vaccine response10

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  • human studyThymosin alpha 1 used as a means of curbing morbidity and mortality in sepsis and numerous infections10

  • human studyClinical studies of Tα-1 combined with entecavir on the treatment of HBV-cirrhosis are ongoing13

  • animalThymic involution has been treated with thymosin alpha 122

  • animalThymosin alpha 1 was used to attempt to reverse thymic involution in hydrocortisone-treated, aged mice22

  • expert opinionExpert consensus formed 10 recommendations on the application of Tα1 in treatment of liver diseases, viral infections, bacterial infections and critical illnesses1

  • expert opinionThymosin alpha 1 has been utilized in the treatment of immunocompromised states and malignancies5

  • expert opinionThymosin alpha 1 has been used as an enhancer of vaccine response5

  • expert opinionThymosin alpha 1 has been used as a means of curbing morbidity and mortality in sepsis and numerous infections5

  • expert opinionThe synthetic version, thymalfasin, is sold under the brand name Zadaxin and is approved in more than 35 countries for chronic hepatitis B, chronic hepatitis C, and as an immune adjunct in cancer care6

  • expert opinionTα1 seems to be a promising alternative adjuvant therapy for sepsis11

  • expert opinionTa1 would be expected to show utility for treatment of immune suppression, whether related to aging or to diseases such as infection or cancer12

  • expert opinionTA1 may be useful as monotherapy for hepatitis B or in combination with IFN-alpha 2b for hepatitis C16

  • expert opinionThymosin alpha-1 is a synthetic thymic peptide used to improve immune responses in times of need17

  • expert opinionThymosin α1 (Tα1) is an immunostimulatory peptide that is commonly used as an immune enhancer in viral infectious diseases such as hepatitis B, hepatitis C, and acquired immune deficiency syndrome (AIDS)18

  • expert opinionIt represents a promising therapeutic approach to counteract age-related immune dysfunction and inflammation, potentially by slowing the aging process.19

  • expert opinionEndocrine influences from thymic hormones including thymosin alpha 1 decline with age and are associated with thymic menopause and cellular immune senescence24

  • expert opinionThymosin Alpha 1 is a natural peptide that helps the immune system fight infection25

  • expert opinionIt has demonstrated significant therapeutic potential in treating viral infections, immunodeficiency conditions, and certain cancers25

  • expert opinionRestoration of immune competence in immunocompromised individuals25

  • expert opinionThe synthetic version is known commercially as Zadaxin (thymalfasin) and has been approved in over 35 countries for treating hepatitis B, hepatitis C, and as an immune adjuvant in cancer therapy25

  • expert opinionThymosin alpha-1 is a research peptide of interest in multiple clinical areas, including hepatology, oncology, immunology, and neurology26

  • expert opinionThymosin alpha-1 is also undergoing evaluation as a vaccine adjuvant and treatment for bacterial and fungal infections26

  • expert opinionThymosin alpha-1 has a long history of development and regulatory evaluation and first attracted interest as a possible immunodeficiency therapy and as a vaccine adjuvant26

  • expert opinionThymosin alpha-1 might be able to help with autoimmune diseases27

  • expert opinionThymosin alpha-1 might be able to help with chronic viral hepatitis27

  • expert opinionThymosin alpha-1 might be able to help with systemic inflammation27

  • expert opinionThymosin alpha-1 may promote better outcomes for cancer, Lyme disease, sepsis, and allergies due to potential to modulate the immune system27

  • expert opinionThymomimetic peptides like thymosin alpha 1 alone or in conjunction with interleukins may augment pathogen and tumor resistance28

Other findings

Based on 1 human trial finding and 4 expert opinion findings.

  • human trialTA1 is a synthetic polypeptide16

  • expert opinionSepsis is a heterogeneous clinical syndrome, making it impossible to generalize clinical results to all septic patients11

  • expert opinionPresent studies on Tα1 treatment are not focused on immunosuppressive individuals11

  • expert opinionThymosin Alpha 1 was first isolated from thymic tissue in 1977 by Allan Goldstein and colleagues at the George Washington University School of Medicine25

  • expert opinionTa1 consists of 28 amino acids and is found in the thymus gland26

Points of contention

Where the evidence is unsettled, thin, or says less than the popular claim — worth knowing before you draw conclusions.

Contested

Sepsis mortality benefit disappears in higher-quality analyses

A meta-analysis of 11 RCTs found a significant 28-day mortality reduction with Tα1 (OR 0.73, P=0.003), but analyses restricted to high-quality RCTs (OR 0.82, P=0.09) and multi-center subgroups (OR 0.86, P=0.20) showed no significant benefit; 75% of patients came from two large RCTs, the large TESTS trial (1106 patients) found no mortality or clinical improvement, and trial sequential analysis suggests the sample size is still inadequate.

Contested

Hepatitis C combination efficacy is inconsistent across trials

One review reports combination TA1 plus IFN-alpha 2b improved ALT normalization (71% vs 35%) and HCV RNA clearance (65% vs 29%), yet also notes another hepatitis C trial found no significant difference in ALT normalization between TA1 and placebo; a tier 3 source states interferon-combination trials have not provided definitive evidence of efficacy.

Contested

Regulatory approval status differs by country

Sources agree thymalfasin/Zadaxin is approved in over 35 countries for hepatitis B, hepatitis C and cancer immune adjunct, but it is not FDA-approved in the United States and is under review for the 503A bulk drug substances list.

Limited evidence

COVID-19 recovery findings were not statistically significant and from a small trial

The COVID-19 RCT enrolled only 49 patients; the higher clinical recovery incidence in both low-flow and high-flow oxygen subgroups did not reach statistical significance, and only the CD4+ T-cell increase reached significance (P=.01).

Single source

Pharmacokinetic values reported by one review only

The peak serum concentration within 2 hours, ~2 hour serum half-life, and return to baseline within 24 hours are reported by a single review (PubMed 11381492).

Other

Dosing ranges vary widely between sources

The core validated protocol is 1.6 mg twice weekly, but tier 3 sources cite ranges up to 6.4 mg twice weekly and daily dosing regimens, and the vaccine trial used 3.2 mg and 6.4 mg doses; higher doses are less well substantiated.

Safety and side effects

Safety and Tolerability

A regulatory document reports that thymosin alpha-1 is safe at recommended dosages and, since 1979, has been well tolerated with a very favorable toxicity profile in more than 3,000 individuals treated — including patients with decompensated liver disease, renal disease requiring hemodialysis, and primary immunodeficiency. A review reports it is well tolerated, with most studies observing only local irritation at the injection site.

Reported Adverse Effects

  • The regulatory document notes that injection-site redness and pain may occur.
  • Rare adverse reactions listed include erythema, transient muscle atrophy, polyarthralgia combined with hand edema, and rash.
  • A transient increase in ALT to more than twice baseline can occur during therapy, per the same document.
  • A web source lists injection-site reactions, headache, nausea and vomiting, and fatigue as risks.

Cautions

The regulatory document advises caution in pregnant or nursing women, states it should not be used in individuals being deliberately immunosuppressed, and notes that pediatric safety has not been established.

Trial Safety Data

The COVID-19 RCT reported nine serious adverse events among treated patients that were deemed not related to Tα1. The H1N1 influenza-vaccine trial (94 patients ITT, 99 in the safety population) reported no adverse events related to thymosin alpha 1 or the vaccine, no effect on hematology or blood-chemistry values, and concluded it was safe and well tolerated. A web source also reports that Thymosin Alpha 1 does not appear to induce receptor downregulation or tachyphylaxis with extended use.

Reconstitution and handling

Dosing

No dose has been established by U.S. regulators for this compound. Sources agree thymalfasin (Zadaxin) is approved in over 35 countries but is not FDA-approved in the United States. The figures below are what sources report — including approved-country labels, clinical trials and vendor/clinic protocols — not guidance.

Core clinical protocol (hepatitis B/C)

  • Tier-1 reviews and approved-country labels report the standard clinical schedule is 1.6 mg subcutaneously twice weekly for 6 to 12 months; a tier 4 dosing guide adds that almost every published TA1 dose traces to this one core protocol across chronic hepatitis B and C trials, with doses spaced 3–4 days apart.
  • A review similarly reports subcutaneous administration twice weekly at 1.6 mg or 900 micrograms/m², as monotherapy for hepatitis B or in combination with IFN-alpha 2b for hepatitis C.
  • A regulatory document lists a general subcutaneous dosage of 1.6 mg twice weekly for 6–12 months (from a 3 mg/mL, 5 mL vial), with 1.5 mg every 3rd day also cited.
  • Low body weight adjustment: for adults under 40 kg (88 lb), an approved-country label cited by a tier 4 dosing guide gives an adjustment of 40 mcg/kg twice weekly — e.g., ~1.2 mg twice weekly at 30 kg and ~1.4 mg at 35 kg.

Reported durations

  • The regulatory document recommends 2 weeks for viral infection and 3 months or longer for HIV, cancer, hepatitis B or C, or complicated immune suppression/over-activation.
  • A dosing protocol cites chronic hepatitis B monotherapy of 6 months (Zadaxin pooled analysis of 3 RCTs), chronic hepatitis C with interferon of 6–12 months, and severe sepsis (TESTS, BMJ 2025) dosing of 7 days continuous every 12 hours in a Phase 3 RCT across 22 Chinese centers.

Higher and wider ranges (less substantiated)

  • A web source lists standard dosing ranging from 1.6 mg to 6.4 mg subcutaneously two to three times weekly, with observable immune benefits often emerging within 2–4 weeks.
  • Another web source lists a common starting dose of 1.6 mg twice weekly for general immune support, with initial-phase regimens of 1.6 mg daily or 3.2 mg twice weekly potentially extending to 6.4 mg twice weekly in severe cases under medical supervision.
  • The H1N1 vaccine trial used 3.2 mg and 6.4 mg doses. Higher doses are chiefly reported by tier-3 web sources and are less well substantiated than the core 1.6 mg protocol, which rests on tier-1 evidence, though the tier-1 H1N1 vaccine trial used 3.2 mg and 6.4 mg doses.

Reconstitution Arithmetic

A dosing protocol notes that from a 10 mg vial reconstituted with 2 mL bacteriostatic water (5 mg/mL), a 1.6 mg dose equals 0.32 mL, or 32 units on a U-100 insulin syringe. The regulatory document references a 3 mg/mL, 5 mL vial format. Administration across sources is subcutaneous.

Sources

Ordered by evidence quality — the strongest first.

  1. Expert Consensus on the Clinical Application of Thymosin Alpha 1 in Infectious Diseases and Critical Care Medicine(opens in a new tab)
    Tier 1Web · journals.lww.com
  2. The efficacy and safety of thymosin α1 for sepsis (TESTS): multicentre, double blinded, randomised, placebo controlled, phase 3 trial(opens in a new tab)
    Tier 1Web · pmc.ncbi.nlm.nih.gov
  3. The efficacy of thymosin alpha 1 for severe sepsis (ETASS): a multicenter, single-blind, randomized and controlled trial(opens in a new tab)
    Tier 1Web · pmc.ncbi.nlm.nih.gov
  4. Thymosin alpha 1: A comprehensive review of the literature(opens in a new tab)
    Tier 1Web · ncbi.nlm.nih.gov
  5. Thymosin alpha 1: A comprehensive review of the literature(opens in a new tab)
    Tier 1Web · pmc.ncbi.nlm.nih.gov
  6. Thymosin Alpha-1 (TA1) Peptide Guide: Dosage, Reconstitution & Side Effects(opens in a new tab)
    Tier 1Web · peptidedosingprotocols.com
  7. Frontiers | Efficacy of thymosin α1 for sepsis: a systematic review and meta-analysis of randomized controlled trials(opens in a new tab)
    Tier 1Web · frontiersin.org · 2025
  8. A Pilot Trial of Thymalfasin (Thymosin-α-1) to Treat Hospitalized Patients With Hypoxemia and Lymphocytopenia Due to Coronavirus Disease 2019 Infection.(opens in a new tab)
    Tier 1PubMed · pubmed.ncbi.nlm.nih.gov · 2023
  9. Thymosin alpha 1: A comprehensive review of the literature(opens in a new tab)
    Tier 1Web · wjgnet.com · 2020
  10. Thymosin alpha 1: A comprehensive review of the literature.(opens in a new tab)
    Tier 1PubMed · pubmed.ncbi.nlm.nih.gov · 2020
  11. Thymosin alpha 1 treatment for patients with sepsis.(opens in a new tab)
    Tier 1PubMed · pubmed.ncbi.nlm.nih.gov · 2018
  12. Immune Modulation with Thymosin Alpha 1 Treatment.(opens in a new tab)
    Tier 1PubMed · pubmed.ncbi.nlm.nih.gov · 2016
  13. Thymosin alpha-1 treatment in chronic hepatitis B.(opens in a new tab)
    Tier 1PubMed · pubmed.ncbi.nlm.nih.gov · 2015
  14. Thymosin-alpha 1 (Zadaxin) enhances the immunogenicity of an adjuvated pandemic H1N1v influenza vaccine (Focetria) in hemodialyzed patients: a pilot study.(opens in a new tab)
    Tier 1PubMed · pubmed.ncbi.nlm.nih.gov · 2012
  15. Utility of thymosin alpha-1 (Zadaxin) as a co-adjuvant in influenza vaccines: a review.(opens in a new tab)
    Tier 1PubMed · pubmed.ncbi.nlm.nih.gov · 2011
  16. Thymosin alpha-1.(opens in a new tab)
    Tier 1PubMed · pubmed.ncbi.nlm.nih.gov · 2001
  17. Thymosin Alpha-1(opens in a new tab)
    Tier 2Web · downloads.regulations.gov
  18. Thymosin α1 and Its Role in Viral Infectious Diseases(opens in a new tab)
    Tier 2Web · mdpi.com
  19. Aging and Thymosin Alpha-1.(opens in a new tab)
    Tier 2PubMed · pubmed.ncbi.nlm.nih.gov · 2025
  20. Thymosin α1 reverses oncolytic adenovirus-induced M2 polarization of macrophages to improve antitumor immunity and therapeutic efficacy.(opens in a new tab)
    Tier 2PubMed · pubmed.ncbi.nlm.nih.gov · 2024
  21. Structures of Thymosin Proteins.(opens in a new tab)
    Tier 2PubMed · pubmed.ncbi.nlm.nih.gov · 2016
  22. Thymic endocrinology.(opens in a new tab)
    Tier 2PubMed · pubmed.ncbi.nlm.nih.gov · 1998
  23. Clinical applications of thymosin alpha-1.(opens in a new tab)
    Tier 2PubMed · pubmed.ncbi.nlm.nih.gov · 1994
  24. Thymic endocrinology.(opens in a new tab)
    Tier 2PubMed · pubmed.ncbi.nlm.nih.gov · 1992
  25. Thymosin Alpha 1: The Thymus Peptide That Strengthens Immunity | Peptidepedia(opens in a new tab)
    Tier 3Web · peptidepedia.org
  26. Thymosin Alpha-1 | Reviews, Clinical Trials, and Safety(opens in a new tab)
    Tier 3Web · peptides.org
  27. Thymosin Alpha-1 | Safety, Benefits, and More [2026](opens in a new tab)
    Tier 3Web · innerbody.com
  28. T-cell adjuvants.(opens in a new tab)
    Tier 3PubMed · pubmed.ncbi.nlm.nih.gov · 1994
  29. Thymosin Alpha 1 Dosage Logic, Half-Life, and ...(opens in a new tab)
    Tier 4Web · tnempower.org