Thymosin alpha-1 (thymalfasin, Zadaxin) peptide: what 65 randomized trials found, where it is approved, and what the gray-market vials rest on
What 1,079 indexed publications and 65 randomized trials actually state about thymosin alpha-1, sentence by sentence, each tied to its source and labeled by the kind of evidence it is.
At a glance
What thymosin alpha-1 is, and what the trials found
Thymosin alpha-1 is a peptide in the immunomodulators & host defense class (thymic peptide; TLR-mediated immunomodulation). Europe PMC indexes 1,079 publications naming it or a listed alias in a title or abstract, including 65 randomized controlled trials and 61 clinical trials of any design, as of . The strongest evidence tier in that literature is human clinical trials.
This page reports what those studies state, sentence by sentence, with each statement tied to its source and labeled by the kind of evidence it is. It does not recommend use, and it does not translate study doses into anything personal.
What the evidence level means
Publication counts show what is indexed, not how strong the evidence is. The ledger below separates human clinical records from preclinical, analytical, and in-vitro work.
Interpretation boundary: An indexed publication count is a discovery measure. It does not establish efficacy, safety, approval, or a personal treatment plan.
Thymosin alpha-1 in two minutes
What it is. A 28-amino-acid immune-regulating peptide from the thymus, isolated in 1972 and sold synthetically as thymalfasin (Zadaxin). Approved in about 35 countries for hepatitis B and C and as an immune adjuvant; never approved in the United States, where it is a research chemical on FDA's compounding category 2 list.
What the research actually shows. 1,079 indexed publications and 65 randomized trials, more than any peptide on this site. The two largest and best-designed, 1,106 septic adults in 2025 and 508 with severe pancreatitis in 2022, found no benefit on their primary endpoints. A 2013 sepsis trial of 361 found a marginal mortality reduction; a 2006 hepatitis B trial found a sustained response of 48% against 27% for interferon; a 2018 cirrhosis trial found no difference in outcomes; cancer trials show immune-marker changes and small uncontrolled response signals.
Safety. In the large placebo-controlled trials, nothing differed from placebo. Better tolerated than interferon. Injection-site redness is the common complaint.
The dose. 1.6 mg subcutaneously, twice a week on the label and for months in hepatitis, or every 12 hours for a week in intensive care.
Where the evidence is thinnest. Everything it is bought for in the United States: immune support in healthy people, long COVID, Lyme disease and autoimmune conditions, none of which has a trial.
Editorial synthesis Written from general pharmacology, the development record and what is commonly reported; not a cited finding. Cited findings on this page carry their own tier.
How it works
Written from general pharmacology and the development record, and marked as editorial synthesis; the measurements behind it are quoted in the biomarker section.
- Editorial synthesis from general knowledge
- Editorial synthesis from general knowledge
- Editorial synthesis from general knowledge
Trial by trial: what thymosin alpha-1 did, and did not do
The randomized and controlled human studies in the ledger, largest first. Read the primary-endpoint column.
| Trial | Participants | Dose and duration | Primary endpoint | Result |
|---|---|---|---|---|
| TESTS (Wu 2025, BMJ) | 1,106 adults with sepsis, 22 Chinese ICUs | 1.6 mg SC every 12 h, 7 days, vs placebo | 28-day mortality | No effect: 23.4% vs 24.1%; no secondary or safety outcome differed |
| TRACE (Ke 2022) | 508 adults with predicted severe necrotising pancreatitis, 94% in ICU | 1.6 mg SC every 12 h for 7 days then daily for 7, vs placebo | Infected pancreatic necrosis | No effect: 15.7% vs 18.1%; no difference in organ failure |
| TRACE post hoc (Huang 2024) | 502 of the above, by metabolic subgroup | As above | Infected necrosis at 90 days | Benefit in the hyperglycaemic subgroup only (18.8% vs 29.7%); hypothesis-generating |
| Colorectal cancer perioperative (Niu 2024) | 400 patients having curative resection with XELOX | 1.6 mg SC twice or three times a week, vs chemotherapy alone | Perioperative immune function; long-term prognosis | Both schedules improved immune markers per the abstract; prognosis detail in full text |
| ETASS (Wu 2013) | 361 adults with severe sepsis, 6 Chinese hospitals | Thymosin alpha-1 vs conventional care (single-blind) | 28-day mortality | 26.0% vs 35.0%, relative risk 0.74, marginal (p 0.049 to 0.062); HLA-DR recovered faster |
| Entecavir combination in cirrhosis (Wu 2018) | 351 with HBV-related compensated cirrhosis | Entecavir with or without thymosin alpha-1; median 38 months follow-up | Decompensation, liver cancer or death | No difference; a trend to fewer liver cancers |
| COVID-19 prevention in dialysis (Tuthill 2023) | 194 haemodialysis patients, United States | Thymalfasin vs control | Infection and morbidity (preliminary report) | 3 deaths on treatment vs 7 in controls, 5 vs 7 serious events; preliminary, most participants vaccinated during the study |
| Hepatitis B vs interferon (You 2006) | 62 with chronic hepatitis B | 1.6 mg SC twice a week for 6 months, vs interferon alpha | Complete response (ALT, HBV DNA, HBeAg) | 31% vs 45% at end of treatment; 48% vs 27% six months later (not significant); better tolerated |
| Gastric cancer neoadjuvant (Xu 2026) | 30 with stage III gastric cancer | 9 weeks with anti-PD-1 and SOX chemotherapy | Pathological complete response | 30% complete, 57% major response; single-arm, no control |
| Radiotherapy combinations (Yu 2025; Zhou 2026) | 37 and 34 with advanced or bulky tumours | Twice weekly with PD-1 inhibitor, GM-CSF and radiotherapy | Response and safety | Response rates reported; single-arm; thymosin's contribution not separable |
| Severe acute pancreatitis pilot (Wang 2011) | 24 patients | 3.2 mg SC twice a day, 7 days | Immune markers; infection | Faster HLA-DR recovery; fewer positive cultures |
| Lung cancer chemoimmunotherapy (Garaci 1995) | 56 with advanced NSCLC | With cisplatin, etoposide and interferon | Response; immune markers | 24 responses; immune suppression by chemotherapy blunted; no control arm |
The two trials that meet modern standards, double-blind, placebo-controlled, powered and pre-registered, are the negative ones. The approvals in 35 countries rest on the hepatitis work of the 1990s and 2000s, most of it not in this ledger, and on a regulatory culture that accepts immune-marker evidence.
Editorial synthesis Written from general pharmacology, the development record and what is commonly reported; not a cited finding. Cited findings on this page carry their own tier.
What the evidence shows
One row per primary study in this record's ledger. Fields are read from each paper's indexing and abstract. "Analytical method" marks papers about detecting or measuring the compound rather than about its effects.
| Study | Design | n | Species | Dose | Route | Duration | Reported outcome | Tier |
|---|---|---|---|---|---|---|---|---|
| Zhou 2026 | Randomized controlled trial | 34 | Humans | — | — | 0 months | Among the 37 treatment courses in 34 patients, 4 patients did not complete the planned therapy, and 1 was lost to follow-up. | Human clinical trial |
| Xu 2026 | Phase 2 clinical trial | — | Humans | — | — | 21 day; 9 weeks | Flow cytometry showed expansion of CD8⁺ T cells with increased CD69 expression and a concurrent reduction in HLA-DR-positive T cells, suggesting dynamic remodeling from broad systemic activation toward a more focused… | Human clinical trial |
| Yu 2025 | Phase 2 clinical trial | 6 | Humans | — | — | 14 days; 3 weeks | Patients who achieved a partial response were significantly more likely to have an abscopal effect( P = 0.025). | Human clinical trial |
| Wu 2025 | Randomized controlled trial | 552 | Humans | — | subcutaneous | 85 years | No secondary or safety outcome differed statistically significantly between the two groups. | Human clinical trial |
| Huang 2024 | Randomized controlled trial | 502 | Humans | — | — | — | Tα1 therapy was associated with reduced incidence of IPN among patients with hyperglycemia (18.8% vs 29.7%: hazard ratio, 0.80; 95% confidence interval, 0.37 to 0.97; p=0.03), but not in the other subgroups. | Human clinical trial |
| Niu 2024 | Randomized controlled trial | 100 | Humans | — | — | — | The conventional-dose and high-dose thymalfasin for injection effectively improves the perioperative immune function of CRC patients and reduces the incidence of postoperative complications, as an effective treatment… | Human clinical trial |
| Tuthill 2023 | Randomized controlled trial | 194 | Humans | — | — | 8 weeks; 8 week | In prior studies, thymalfasin (thymosin alpha 1, Ta1) has been shown to enhance antibody response to influenza vaccine and reduce influenza infection in geriatric populations, including hemodialysis patients, when used… | Human clinical trial |
| Ke 2022 | Randomized controlled trial | 508 | Humans | — | — | 7 days | There was no difference in other major complications, including new-onset organ failure (10.6% vs. 15%), bleeding (6.3% vs. 3.5%), and gastrointestinal fistula (2% vs. 2.4%). | Human clinical trial |
| Wu 2018 | Randomized controlled trial | 351 | Humans | — | — | 52 weeks; 26 weeks | There was no significant difference between two groups in endpoint events, while combination therapy with Ta-1 has a tendency to inhibit the development of HCC. | Human clinical trial |
| Wu 2013 | Randomized controlled trial | 180 | Humans | — | — | — | Greater improvement of mHLA-DR was observed in the Tα1 group on day 3 (mean difference in mHLA-DR changes between the two groups was 3.9%, 95% CI 0.2 to 7.6%, P = 0.037) and day 7 (mean difference in mHLA-DR changes… | Human clinical trial |
| Wang 2011 | Randomized controlled trial | 24 | Humans | — | — | — | The positive rates of blood and abdominal drainage culture were statistically significant during the 28th follow-up period. | Human clinical trial |
| You 2006 | Randomized controlled trial | 30 | Humans | — | subcutaneous | 12 mo; 6 mo | Compared with the results observed in the historical control (HC) group untreated with IFN-alpha which was followed up for 12 mo, the rate of complete response was significantly higher in IFN-alpha group at the end of… | Human clinical trial |
| Garaci 1995 | Phase 3 clinical trial | — | Humans | — | — | 3 weeks | — | Human clinical trial |
| Bistoni 1982 | Animal study | — | Mice | — | intravenous | — | Significant resistance ot lethal infection was afforded by 100 micrograms of thymosin alpha 1 per kg given before or before and after challenge, whereas no protection was found in mice treated with thymosin alpha 1… | Animal, preclinical |
| Liu 2025 | In vitro study | 330 | Humans | — | — | — | By targeting post-operative immune system imbalance, this study aims to establish a novel therapeutic approach for reducing systemic inflammatory response syndrome (SIRS)-mediated organ injury and improving long-term… | Mechanistic, in vitro |
| Vitek 2025 | In vitro study | — | — | — | subcutaneous | 2 weeks | We initially selected specified ingredients, with ethanol serving to reduce viscosity and stabilize the peptide drug Tα1, lecithin contributing to LCCs formation and stabilization, and glycerol monooleate or glycerol… | Mechanistic, in vitro |
| Ricci 2023 | In vitro study | 19 | Humans | — | — | — | Moving from ex vivo data showing an enhancement in the frequency of inflammatory monocytes and activated mDC in COVID-19 patients, a PBMC-based experimental setting reproduced in vitro a similar profile with an… | Mechanistic, in vitro |
| Zhou 2020 | In vitro study | — | Humans | — | — | 90 days | This study was designed to test the hypothesis that the administration of thymosin alpha 1 during the acute phase of ANP will result in a reduced incidence of IPN. | Mechanistic, in vitro |
Doses reported in studies
Each entry is a sentence quoted from the study's abstract, with the study's design, sample size and year in front of it. Comparator doses in the same sentence are not attributed to thymosin alpha-1.
- Source
pmid-39814420 - Source
pmid-35713670 - Source
pmid-17075991 - Source
pmid-20549321 - Source
pmid-37248723 - Source
pmid-7085074
Every thymosin alpha-1 dose in the trials, in one table
Every figure here is a licensed or trial dose. Gray-market vials print the same 1.6 mg; the difference is what is in them.
| Setting | Route | Dose | Schedule | Population |
|---|---|---|---|---|
| Zadaxin label (approving countries) | Subcutaneous | 1.6 mg | Twice a week, 6 to 12 months | Chronic hepatitis B and C |
| Hepatitis B trial (2006) | Subcutaneous | 1.6 mg | Twice a week, 6 months | Chronic hepatitis B |
| Sepsis phase 3 (2025); pancreatitis (2022) | Subcutaneous | 1.6 mg | Every 12 hours for 7 days (then daily for 7 in pancreatitis) | Intensive-care patients |
| Severe pancreatitis pilot (2011) | Subcutaneous | 3.2 mg | Twice a day, 7 days | 24 patients |
| Colorectal cancer (2024) | Subcutaneous | 1.6 mg | Twice or three times a week, perioperative | 400 surgical patients |
| Cancer combination trials (2025 to 2026) | Subcutaneous | Not stated in the abstracts | Twice weekly; 9 weeks | Advanced or resectable tumours |
| Mice (1982) | Intravenous | 100 micrograms | Single | Candida infection model |
Nothing on this page is an instruction to take anything. The point of the table is that the dose is not the variable: the same 1.6 mg failed in sepsis at one schedule and helped in hepatitis at another, and the vials sold in the United States carry the number without the licence, the pharmacist or the indication.
Editorial synthesis Written from general pharmacology, the development record and what is commonly reported; not a cited finding. Cited findings on this page carry their own tier.
Side effects: what randomized trials of 1,100 people recorded
From randomized placebo-controlled trials with hundreds of participants: no safety outcome differed from placebo in the sepsis or pancreatitis trials, and hepatitis trials called it better tolerated than interferon. Injection-site redness is the common complaint. Events and their frequency as each study reported them, with the denominator where the abstract gives one.
- Source
pmid-39814420 - Source
pmid-35713670 - Source
pmid-17075991 - Source
pmid-30063860 - Editorial synthesis from general knowledge · primary document to be added to the ledger
Who thymosin alpha-1 is discussed for, and the cautions that recur
Licensed for: chronic hepatitis B and C, and as an immune adjuvant, in about 35 countries. Trialled in: sepsis, severe pancreatitis, cancer alongside chemotherapy or radiotherapy, cirrhosis, dialysis patients during COVID-19. Community: people seeking immune support, and people with long COVID, Lyme disease, chronic fatigue or autoimmune disease.
The cautions come from the label's contraindications and from where the evidence stops:
- Deliberate immunosuppression. The label excludes transplant recipients on immunosuppressants: a drug that primes T cells works against the treatment.
- Autoimmune disease. Not a trial population and a mechanistic concern; forum reports of flares match the prediction. The label's regulator, not a vendor, is the source to read.
- Healthy people. Every trial enrolled the seriously ill, whose immune markers were abnormal. What the peptide does to a normal immune system over months is unstudied.
- Expecting the sepsis or pancreatitis result. Both large trials were negative; a clinic citing 'sepsis trials' is citing the 2013 result and not the 2025 one.
- Cancer. Trials used it as an adjunct to chemotherapy, immunotherapy or radiotherapy in supervised settings; it is not a cancer treatment on its own and no trial tested it as one.
- Pregnancy and children. Not studied in the ledger's trials.
Editorial synthesis Written from general pharmacology, the development record and what is commonly reported; not a cited finding. Cited findings on this page carry their own tier.
Biomarkers measured in studies
Laboratory and clinical measures the studies report tracking, including which hormones did and did not change.
-
Treatment included three 21-day cycles of serplulimab (anti-PD-1) plus SOX (S-1 and oxaliplatin) and 9 weeks of thymalfasin, followed by curative gastrectomy.
Sourcepmid-41749205· quoted verbatim from the abstract -
The peculiar property of Thymosin alpha 1 (Tα1) to act as master regulator of immune homeostasis has been successfully defined in different physiological and pathological contexts ranging from cancer to infection.
Sourcepmid-36933449· quoted verbatim from the abstract
Reported interactions
Sentences in which the compound is studied alongside another agent. Read the quotation: the word interaction can also be statistical.
-
We conducted a phase II trial to evaluate anti-PD-1 plus SOX (S-1 and oxaliplatin) immunochemotherapy combined with thymalfasin as neoadjuvant treatment for G/EGJ adenocarcinoma.
Sourcepmid-41749205· quoted verbatim from the abstract
Reported timelines
Onset, peak and duration figures as each study reported them.
- Source
pmid-23327199 - Source
pmid-17075991 - Source
pmid-32994239
What is measured over time, and what is not
The peptide clears in about two hours, by the label, and its effects are measured in days and months. In sepsis the immune marker HLA-DR recovered faster by day 3 and mortality was counted at 28 days, where the large trial found nothing. In pancreatitis the outcome was infected necrosis over the index admission and 90 days. In hepatitis B the response kept rising for six months after treatment ended, the clearest sign that the effect is immune rather than directly antiviral. The cirrhosis trial followed people for 38 months and found no difference in hard outcomes. Nothing has been measured in healthy people over any period, so 'how long until I feel it' has no answer in the literature; the trials did not ask how anyone felt.
Editorial synthesis Written from general pharmacology, the development record and what is commonly reported; not a cited finding. Cited findings on this page carry their own tier.
Study durations
Treatment and follow-up periods as stated in each abstract.
- Source
pmid-39814420 - Source
pmid-30063860 - Source
pmid-41749205
Routes: subcutaneous injection in every trial and on the label
Subcutaneous injection in every human trial and in the licensed product. Nothing else has been studied in people; the intravenous route appears only in a 1982 mouse study. Routes of administration named in each study.
- administration by subcutaneous route reported
A stratified block method was used for randomisation, and participants were stratified by age ( Interventions Subcutaneous injection of thymosin α1 or placebo every 12 hours for seven days unless discontinued owing to discharge from the intensive care unit, death, or withdrawal of consent.
Sourcepmid-39814420· quoted verbatim from the abstract - administration by subcutaneous route reported
The patients in group A received subcutaneous injection of 1.6 mg thymosin-alpha1, twice a week (T-alpha1 group) for six months, and the patients in group B received 5 MU interferon alpha (IFN-alpha) each day for fifteen days, then three times weekly (IFN-alpha group) for six months.
Sourcepmid-17075991· quoted verbatim from the abstract - administration by intravenous route reported
Two- to four-month-old mice were treated with graded doses of thymosin alpha 1 before, after, or before and after intravenous challenge with C. albicans.
Sourcepmid-7085074· quoted verbatim from the abstract - administration by subcutaneous route reported
In this study, we thus aimed to exploit the potential of a liquid crystalline platform for the sustained release of peptide drug thymosin alpha 1 (Tα1), characterized by a short plasma half-life and with that associated twice-weekly SC administration regimen.
Sourcepmid-40066714· quoted verbatim from the abstract
What people report outside the literature
Forum reports describe use for 'immune support', long COVID, Lyme disease, chronic fatigue and autoimmune conditions, at the licensed dose from unlicensed vials. None of those uses has a trial behind it. What circulates in user communities and clinic marketing, reported so a reader knows the figures and their origin. None of it has been tested in a trial, and none of it is a suggestion.
- Editorial synthesis from general knowledge
Reconstitution mathematics
Lyophilised peptide is supplied as a mass in a vial and dissolved in a stated volume of diluent. Two figures follow from that and nothing else:
- Concentration = mass in vial ÷ diluent volume. A 5 mg vial in 2 mL is 2.5 mg/mL, or 2,500 mcg/mL.
- Volume for a given mass = that mass ÷ concentration. 250 mcg at 2,500 mcg/mL is 0.1 mL. On a U-100 insulin syringe, where 1 mL is 100 units, that is 10 units.
Study doses on this page are quoted as published, in the units the authors used. Converting between mcg, mg and IU, or between a mass and a syringe volume, is arithmetic; deciding a mass is not, and this page does not do it. The reconstitution calculator performs the conversion with the formula shown.
Reading a certificate of analysis
A certificate of analysis is a laboratory report on one batch. Reading it means checking four things in order.
- Identity. Mass spectrometry should report an observed molecular mass matching the peptide's theoretical mass within the instrument's stated tolerance. A certificate with no mass spectrometry, or one that lists only the expected value, has not confirmed identity.
- Purity. HPLC purity is the area of the main peak as a share of all peaks, at a stated wavelength. It says nothing about what the other peaks are, and it is not a measure of quantity.
- Quantity. Net peptide content, by amino acid analysis or UV, is the fraction of the vial's mass that is peptide rather than counter-ions and water. A 5 mg vial at 80% net content holds 4 mg of peptide, and every concentration figure above changes accordingly.
- Provenance. The batch number on the certificate should match the vial, the laboratory should be named and independent of the seller, and the test date should be recent.
This page rates no supplier and links to none. It describes how to read the document.
Equipment described in studies
Published human studies of injectable peptides report the same small set of materials: single-use insulin syringes with fixed needles, most often U-100 with 29 to 31 gauge needles; bacteriostatic water or sterile water for injection as diluent, with the choice stated in the methods; alcohol swabs; and refrigerated storage of reconstituted solution. Animal studies more often report intraperitoneal or intragastric administration and state the vehicle used. Where a study in this record's ledger names its materials or vehicle, that sentence appears under storage or routes above; where it does not, nothing is assumed here.
Storage and handling
The licensed product is supplied as a lyophilised powder with a diluent, stored refrigerated and reconstituted immediately before subcutaneous injection, under instructions in the approving countries' product information. Vials sold in the United States are not that product; their content and stability are unverified.
Editorial synthesis Written from general pharmacology, the development record and what is commonly reported; not a cited finding. Cited findings on this page carry their own tier.
Common mistakes in how thymosin alpha-1 is discussed
- Citing '35 countries' as if it settled efficacy. The approvals are for hepatitis B and C and as an adjuvant, from older evidence; the largest modern trials, in intensive care, were negative.
- Quoting the 2013 sepsis trial without the 2025 one. ETASS found a marginal benefit in 361 patients; TESTS found none in 1,106. The second was designed to confirm the first.
- Confusing it with TB-500. Different thymosin, different molecule, different purpose, and TB-500 has no human trial. The shared word comes from the 1970s thymus extracts.
- Treating immune-marker changes as clinical benefit. HLA-DR, CD4 counts and cytokine shifts move reliably; mortality and infection rates did not in the trials built to test them.
- Reading the FDA category 2 listing as a safety verdict. It was a compounding decision about evidence sufficiency for US pharmacies, made about a drug licensed elsewhere; the safety record in trials is clean.
- Assuming a vial equals Zadaxin. The licensed product has a manufacturer, a regulator and a pharmacist; a research-chemical vial has a label.
Editorial synthesis Written from general pharmacology, the development record and what is commonly reported; not a cited finding. Cited findings on this page carry their own tier.
Thymosin alpha-1 vs TB-500 (thymosin beta-4), LL-37 and interferon
| Compound | What it is | Human evidence | Status |
|---|---|---|---|
| Thymosin alpha-1 | 28-amino-acid immune-regulating peptide; 1,079 indexed publications | 65 randomized trials; two large negative ICU trials; hepatitis approvals | Approved in about 35 countries; not in the US; FDA category 2 (2023) |
| TB-500 | Fragment of thymosin beta-4, an actin-binding repair protein; 1257 indexed publications | 14 human studies of the fragment in its ledger; thymosin beta-4 itself in small trials | Not approved; WADA S2 |
| LL-37 | Human antimicrobial peptide of the innate immune system; 2826 indexed publications | 23 human studies in its ledger, none as a treatment | Not approved; research chemical |
| Interferon alpha | The comparator in the hepatitis B trial | Decades of trials; approved for hepatitis and cancers; flu-like toxicity | Approved worldwide; no record on this site |
| BPC-157 | Gastric repair pentadecapeptide often stacked with TA1; 228 indexed publications | 2 small uncontrolled human studies | Not approved; WADA S0 |
The search 'thymosin alpha 1 vs thymosin beta 4' compares an approved immune drug with an unapproved repair fragment that shares a word. The comparison with interferon is the one that was actually run, and thymosin alpha-1 won it on tolerability and lost on end-of-treatment response.
Editorial synthesis Written from general pharmacology, the development record and what is commonly reported; not a cited finding. Cited findings on this page carry their own tier.
Exclusion criteria in studies
Who each trial excluded, as stated in the abstract.
-
520 eligible patients with ANP will be randomised in a 1:1 ratio to receive either the thymosin alpha 1 or the placebo using the same mode of administration.
Sourcepmid-32994239· quoted verbatim from the abstract
Other compounds in its class
Same class in the registry: LL-37. Each row shows what that compound's own record states; nothing is inferred across rows.
| Compound | Tier | Publications | RCTs | Record |
|---|---|---|---|---|
| Thymosin alpha-1 | Human clinical trial | 1,079 | 65 | draft |
| LL-37 | Human clinical trial | 2,826 | 38 | draft |
Regulatory status: approved in 35 countries, not in the United States, and on FDA's category 2 list
Registry facts only. Jurisdiction-level status, compounding categories and sport prohibitions need their own cited documents before they appear here.
- Editorial synthesis from general knowledge · primary document to be added to the ledger
Open questions and limitations
What is genuinely unknown, stated plainly. A missing field is not evidence that the outcome is safe, effective, or established.
- Why the two largest, best-designed trials (sepsis 2025, pancreatitis 2022) were negative while older and smaller trials were positive is unexplained.
- The hepatitis C trials and the 1990s hepatitis B trials behind the foreign approvals are not in the ledger; the Zadaxin product information and FDA's 2023 notice are cited editorially.
- No trial has studied thymosin alpha-1 in healthy people or for any community use (immune support, long COVID, Lyme disease, autoimmune disease).
Questions people ask
What is the half-life of thymosin alpha-1?
About two hours in plasma after subcutaneous injection, by the Zadaxin product information, with peak levels one to two hours after the dose. The immune effects the trials measured lasted days to weeks, which is why the licensed schedule is twice a week and the intensive-care trials dosed every 12 hours for a week. No abstract in the ledger states the half-life; the figure comes from the label, which is not yet a ledger source.
Does thymosin alpha-1 help long COVID?
No trial has tested it for long COVID. During the pandemic it was tried for acute COVID-19, mostly in Chinese observational studies and one small randomized pilot in dialysis patients whose preliminary report counted 3 deaths on treatment against 7 without; a 2023 cell study described effects on innate inflammatory responses. None of that is a long-COVID result.
What is thymosin alpha-1?
Thymosin alpha-1 is a 28-amino-acid peptide first isolated from calf thymus by Allan Goldstein in 1972 and made synthetically as thymalfasin, sold as Zadaxin. It acts on dendritic cells and T cells through Toll-like receptors to shift immune responses, and is approved in about 35 countries for chronic hepatitis B and C and as an immune adjuvant. It is not approved in the United States, where it circulates as a research chemical and was placed on FDA's compounding category 2 list in 2023.
How does thymosin alpha-1 make you feel?
In the trials, mostly nothing noticeable: the placebo-controlled sepsis and pancreatitis trials found no symptom or safety outcome that differed from placebo, and hepatitis trials reported it better tolerated than interferon, whose flu-like effects it lacks. Forum reports describe injection-site redness, occasional fatigue or a 'flu-ish' day after a dose, and, often, no felt effect at all.
Is thymosin alpha-1 the same as TB-500?
No. Thymosin alpha-1 is a 28-amino-acid immune-modulating peptide with 65 randomized trials and approvals in 35 countries. TB-500 is a fragment of thymosin beta-4, a 43-amino-acid actin-binding protein studied for tissue repair, with no human trial of the fragment. They share the word thymosin because both were first isolated from thymus extracts in the 1970s, and nothing else.
Is thymosin alpha-1 FDA approved?
No. Thymalfasin (Zadaxin) is approved in about 35 countries for chronic hepatitis B and C and as an immune adjuvant, but never in the United States, where applications for hepatitis C and melanoma did not succeed. In September 2023 FDA placed it in category 2 of the compounding bulk-substances list, barring pharmacies from compounding it; press reports in 2026 describe a possible further review.
What is the dose of thymosin alpha-1?
The licensed dose is 1.6 mg by subcutaneous injection twice a week, for six to twelve months in hepatitis. Intensive-care trials used 1.6 mg every 12 hours for seven days, a pancreatitis pilot used 3.2 mg twice daily, and a cancer trial compared twice- and three-times-weekly 1.6 mg. Vendor vials print the licensed figure.
Does thymosin alpha-1 work for sepsis?
The best evidence says no. The 2025 TESTS phase 3 in 1,106 septic adults found 28-day mortality of 23.4% on thymosin alpha-1 against 24.1% on placebo, with no secondary or safety outcome differing. The 2013 ETASS trial of 361 had found a marginal reduction (26% vs 35%), which TESTS was designed to confirm and did not.
Does thymosin alpha-1 work for hepatitis B?
In the 2006 randomized trial against interferon alpha, 48% of thymosin-treated patients had a complete response six months after a six-month course, against 27% on interferon, a difference that did not reach significance in 62 patients, with better tolerability. In HBV cirrhosis, adding it to entecavir for two years changed no hard outcome. The approvals in 35 countries rest mainly on hepatitis trials of the 1990s and 2000s.
What are the side effects of thymosin alpha-1?
In the 1,106-person sepsis trial no safety outcome differed from placebo, and the pancreatitis and cirrhosis trials reported the same. It is better tolerated than interferon, lacking its flu-like effects. Injection-site redness is the common complaint; the label's contraindications are deliberate immunosuppression and hypersensitivity.
Who should not take thymosin alpha-1?
By the label, people deliberately immunosuppressed after organ transplantation, and anyone hypersensitive to it. By the evidence, anyone expecting a benefit outside hepatitis: the community uses, including autoimmune disease, have no trials and, for autoimmunity, a mechanism pointing the wrong way.
Is thymosin alpha-1 the same as TB-500 or thymosin beta-4?
No. Thymosin alpha-1 is a 28-amino-acid immune regulator with 65 randomized trials and foreign approvals; TB-500 is a fragment of thymosin beta-4, a 43-amino-acid actin-binding protein studied for tissue repair, with no human trial of the fragment. They share a name from 1970s thymus extracts and nothing else.
What is the half-life of thymosin alpha-1?
About two hours in plasma after subcutaneous injection, by the Zadaxin product information, with peak levels at one to two hours. The immune effects last days to weeks, which is why the licensed schedule is twice weekly. The figure is from the label, not from an abstract in the ledger.
Does thymosin alpha-1 help with COVID-19 or long COVID?
For acute COVID-19, Chinese observational studies and a small US randomized pilot in dialysis patients (preliminary: 3 deaths on treatment vs 7 without, most participants vaccinated during the study) exist, plus cell studies of innate immune effects. For long COVID, no study at all.
Does thymosin alpha-1 treat cancer?
Not on its own, and no trial has tested it that way. It has been given alongside chemotherapy, PD-1 inhibitors and radiotherapy in single-arm trials of 30 to 56 patients with encouraging response rates in which its contribution cannot be separated, and in a 400-patient surgical trial it improved perioperative immune markers. The 2018 cirrhosis trial saw a trend to fewer liver cancers without a change in outcomes.
Is thymosin alpha-1 banned in sport?
It is not named on the WADA Prohibited List, and as a medicine approved abroad it does not fall under the S0 catch-all for unapproved substances the way most research peptides do. The list changes yearly; an athlete should check it and their own federation's rules.
Why is a drug approved in 35 countries sold as a research chemical in the United States?
Because approval is national. SciClone never obtained US approval, so there is no US product, and the only US route, compounding, was closed by FDA's September 2023 category 2 decision. What is sold in the US is therefore an unlicensed copy of a licensed foreign drug, with no pharmacist, indication or quality control attached.
Sources
Full citations. Every claim above links to one of these by its id.
- 1
- 2Neoadjuvant immunochemotherapy plus thymalfasin in locally advanced gastric cancer: a prospective clinical trial.
pmid-41749205· · peer-reviewed - 3Effect of thymosin α1 on Immune response and organ function in acute aortic dissection surgery: PANDA II trial protocol.
pmid-40367062· · peer-reviewed - 4
- 5
- 6
- 7
- 8
- 9
- 10
- 11
- 12
Show the remaining 12 sources
- 13
- 14
- 15The efficacy of thymosin alpha 1 for severe sepsis (ETASS): a multicenter, single-blind, randomized and controlled trial.
pmid-23327199· · peer-reviewed - 16
- 17From lab to bedside: emerging clinical applications of thymosin alpha 1.
pmid-19392576· · peer-reviewed - 18Thymosin alpha1: an endogenous regulator of inflammation, immunity, and tolerance.
pmid-17495242· · peer-reviewed - 19Efficacy of thymosin alpha-1 and interferon alpha in treatment of chronic viral hepatitis B: a randomized controlled study.
pmid-17075991· · peer-reviewed - 20Immunodeficiency and cancer: prospects for correction.
pmid-12860163· · peer-reviewed - 21The thymosins. Prothymosin alpha, parathymosin, and beta-thymosins: structure and function.
pmid-12852257· · peer-reviewed - 22
- 23Immunologic abnormalities in the acquired immunodeficiency syndrome.
pmid-2415141· · peer-reviewed - 24Increase of mouse resistance to Candida albicans infection by thymosin alpha 1.
pmid-7085074· · peer-reviewed
Reference card
- Compound
- Thymosin alpha-1, immunomodulators and host defense
- Evidence tier
- Human clinical trial
- Indexed publications
- 1,079 · 65 RCTs · 61 other clinical trials
- Approval
- not approved · max phase 3
- Routes reported
- intravenous, subcutaneous
- Reviewed
- Adam Mirando, PharmD,
Study figures are as published in each source and are not recommendations. Print or save this card with its date.
Last reviewed and what changed
Newest first. These are the record's own revision dates, and the same dates feed the sitemap.
- · Reviewed by Adam Mirando, PharmD, on 2026-09-29.
- · Written under the sequencing rule after research/intents/thymosin-alpha-1.json: guide (8 sections incl. a twelve-trial table with verdicts), FAQ to 12 plus 6 from the map, dose, duration, timeline and adverse-event claims from the abstracts, mechanism, reported-use, regulatory (approved in 35 countries, not the US, FDA category 2) with pending_source; a hepatitis study of nucleic acid polymers using thymosin as a comparator removed from the evidence table; intent-driven H1 and title.
- · Claims drafted extractively from 24 ledger sources by scripts/draft_claims.py: 19 claims, 19 evidence-table rows. Status researched -> draft.
- · Claims drafted extractively from 24 ledger sources by scripts/draft_claims.py: 36 claims, 19 evidence-table rows. Status researched -> draft.
- · Metadata refreshed by scripts/fetch_evidence.py --refresh-meta: chembl None -> CHEMBL2103979.
- · Evidence fetched from Europe PMC and ChEMBL by scripts/fetch_evidence.py; claims not yet written.