Thymosin α1
A thymic peptide sold as Zadaxin in about 35 countries: mixed hepatitis trials, and no benefit in its largest trial
Thymosin α1 is a 28-amino-acid peptide from the thymus, sold as the drug thymalfasin (Zadaxin) in about 35 countries, mainly for chronic hepatitis B and C. It is meant to restore flagging immune responses. Its largest trial, 1,106 adults with sepsis, found no effect on 28-day mortality, and the hepatitis trials are old and mixed. It has never been approved in the US, and US pharmacies cannot compound it.
What is it?
Thymosin α1 is a 28-amino-acid peptide, acetylated at its start and cut from the larger protein prothymosin α, that occurs naturally in the thymus. Its synthetic form, thymalfasin, is sold as Zadaxin in about 35 countries, chiefly for chronic hepatitis B and C, and it has been tried as an immune booster in cancer, sepsis, HIV, COVID-19 and alongside vaccines. It has never been approved in the US.
Its biggest test was a failure. In TESTS, a double-blind trial across 22 Chinese intensive-care units, 1,106 adults with sepsis received thymosin α1 or placebo every 12 hours for seven days. Twenty-eight-day mortality was 23.4% against 24.1%, a hazard ratio of 0.99, and no secondary or safety outcome differed. Subgroups pointed in opposite directions, with a worse result in patients under 60 and a possible benefit in those with diabetes: signals that would need their own trial before anyone relied on them.
The hepatitis record is older and mixed. In chronic hepatitis B, a 26-week course of 1.6 mg twice weekly cleared the virus in 40.6% of patients by 18 months against 9.4% of untreated controls, yet a 52-week course reached only 26.5%, not significantly better than no treatment. Added to interferon, it raised end-of-treatment response in hepatitis C from 16.2% to 37.1%, and in hepatitis B it nudged HBeAg loss from 28.0% to 45.8%, a difference that did not reach significance.
Elsewhere the evidence is small or uncontrolled. A meta-analysis of eight COVID-19 studies found lower mortality but very high heterogeneity, while a 275-patient retrospective study found no faster T-cell recovery and slower viral clearance. In cancer it has mostly been given with chemotherapy or immunotherapy in single-arm trials, which cannot separate its effect from the other drugs. In the US it was placed in 503A Category 2 in 2023; the nomination was later withdrawn, and FDA's list updated May 14, 2026 names it in no category, so pharmacies cannot compound it.
Mechanism of Action
The abstracts treat thymosin α1 as an immune regulator and measure it through T-cell counts, immune markers and viral responses rather than through a single receptor. Four threads run through them.
The immune changes and the hepatitis B result come from small trials, some without controls. The one large placebo-controlled trial, in sepsis, found no effect on survival.
Each step is tagged with where it was shown. A dashed red arrow marks a link the evidence does not establish.
The pathway in words
- Thymosin alpha 1. A peptide naturally made in the thymus, chemically synthesised as thymalfasin, used to modify and restore immune function. Shown in: review. Source: PubMed 33362999.
- Lower in disease. Serum levels are lower than in healthy people in hepatitis B, psoriatic arthritis, multiple sclerosis and sepsis. Shown in: review. Source: PubMed 30063864.
- Immune cells in people. In 20 people with HIV whose CD4 counts stayed low, the CD4 share rose from 17.2% to 29.1% over 24 weeks; there was no control group. Shown in: people. Source: PubMed 38233816.
- Hepatitis B. In 98 patients, a 26-week course gave a complete virological response at 18 months in 40.6% against 9.4% untreated. Shown in: people. Source: PubMed 9581695.
- tested, no benefit shown. Survival in sepsis. In 1,106 adults with sepsis, 28-day mortality was 23.4% on thymosin alpha 1 against 24.1% on placebo. Shown in: people. Source: PubMed 39814420.
T-cell restoration
In 20 people with HIV whose CD4 counts stayed low despite antiretrovirals, 24 weeks of treatment raised the CD4 share of T cells from 17.2% to 29.1%, raised the share of naive CD4 and CD8 cells and lowered the exhaustion marker PD-1, although CD4 counts at week 24 did not differ significantly from baseline. In COVID-19 patients on low-flow oxygen, CD4 counts rose 3.84 times more by day five than with standard care.
Viral clearance
In chronic hepatitis B, complete responses kept accumulating after treatment stopped: rates were similar across groups at the end of therapy and diverged by 18 months. With interferon in hepatitis C, viral load fell below baseline at weeks 8, 16 and 24, which it did not with interferon alone.
Vaccine responses
In hemodialysis patients, adding 3.2 or 6.4 mg of thymosin α1 to a pandemic H1N1 vaccine improved antibody titres at day 21, and both combined groups met the European licensing criteria for flu vaccines; no adverse event was attributed to thymosin α1.
Low levels in disease
Serum thymosin α1 is significantly lower than in healthy people in hepatitis B, psoriatic arthritis, multiple sclerosis and sepsis, a 2018 review reports, adding that normal baseline levels and the best dose and schedule are still open questions.
Published Research
Our evidence set holds 52 papers on thymosin α1, and 48 name it in their titles. The 15 cards below lead with the controlled trials, negative results included, then the smaller and uncontrolled studies, a product-quality analysis and the reviews. Several reviews are enthusiastic; the controlled trials are less so.
TESTS: sepsis, 1,106 adults
Across 22 Chinese centres, 1,106 adults with sepsis were randomised to thymosin α1 or placebo under the skin every 12 hours for seven days. Twenty-eight-day mortality was 23.4% versus 24.1% (hazard ratio 0.99, 95% CI 0.77 to 1.27, P = 0.93), and no secondary or safety outcome differed. Prespecified subgroups: under 60, hazard ratio 1.67; with diabetes, 0.58.
Chronic hepatitis B, 26 vs 52 weeks
Ninety-eight patients received 1.6 mg twice weekly for 26 weeks, the same for 52 weeks, or no treatment. At 18 months, complete virological response was 40.6%, 26.5% and 9.4% (26 weeks vs control P = .004; 52 weeks vs control P = .068); at the end of therapy the groups had been similar. No responder lost HBsAg, histology improved, and no significant side effects were seen.
Added to interferon in hepatitis B
In a double-blind trial, 98 HBeAg-positive patients took lymphoblastoid interferon for 24 weeks with thymosin α1 (48) or placebo (50). HBeAg loss at 72 weeks was 45.8% versus 28.0%, a 17.8-point difference (95% CI −1.2 to 35.3, P = 0.067), and no secondary endpoint differed.
Added to interferon in hepatitis C
One hundred nine patients received 1.6 mg twice weekly with interferon, interferon with placebo, or double placebo. End-of-treatment biochemical response was 37.1%, 16.2% and 2.7% (combination vs interferon P = .04), and HCV RNA cleared in 37.1% versus 18.9% on interferon alone.
COVID-19 with hypoxemia: open-label pilot
Forty-nine hospitalised patients with low oxygen and low lymphocyte counts were randomised to thymalfasin or standard care. Clinical recovery was more frequent on treatment but not significantly (subdistribution hazard ratios 1.48 and 1.28). On low-flow oxygen, CD4 counts rose 3.84 times more by day five (P = .01). Nine serious adverse events in treated patients were judged unrelated.
COVID-19: no T-cell benefit in 275 patients
In a retrospective study of 275 patients, 126 of them treated, CD4 and CD8 recovery did not differ with or without thymosin α1 (CD4 rise 286 vs 326; CD8 154 vs 170). Viral clearance took longer in treated patients, whether baseline CD4 was normal (14 vs 11 days) or low (15 vs 11 days).
Flu vaccine in hemodialysis patients
Patients on hemodialysis got an adjuvanted pandemic H1N1 vaccine alone or with 3.2 or 6.4 mg of thymosin α1. Both combined groups had better antibody titres and ratios at day 21 and fully met the European licensing criteria; no adverse event was attributed to thymosin α1. The authors call it a pilot needing larger studies.
HIV immune non-responders
Twenty people with HIV whose CD4 counts stayed at 100–350 despite antiretrovirals took 1.6 mg daily for two weeks, then twice weekly to week 24. CD4 counts at week 24 did not differ significantly from baseline, but the CD4 share rose from 17.2% to 29.1%, naive T-cell shares rose, and PD-1 expression fell. There was no control group.
Melanoma, with chemotherapy and IL-2
Forty-six patients with metastatic melanoma received dacarbazine, then thymosin α1 2 mg on days 4 to 7, then interleukin-2, in three-week cycles. Fifteen of 42 evaluable patients (36%) responded, two completely; median survival was 11 months. Side effects came mainly from IL-2. With no control arm, the abstract cannot separate thymosin α1's share.
Gastric cancer, with immunochemotherapy
In a single-arm phase II trial, 30 patients with stage III gastric or gastro-oesophageal junction cancer received serplulimab, S-1 and oxaliplatin plus nine weeks of thymalfasin before surgery. Complete pathological response was 30.0% and major response 56.7%; any-grade adverse events occurred in 93.3%.
Sepsis meta-analysis before TESTS
Five randomised trials with 198 patients, pooled in this Chinese-language review, suggested that thymosin α1 raised CD4 counts and the CD4/CD8 ratio, lowered APACHE II scores and shortened mechanical ventilation. The large placebo-controlled TESTS trial, published in 2025, did not confirm a survival benefit.
COVID-19 meta-analysis
Pooling eight studies of moderate to critical COVID-19, thymosin α1 was linked to lower mortality (risk ratio 0.59, 95% CI 0.37 to 0.93) but with 84% heterogeneity, and it made no difference to mechanical ventilation or length of stay. The mortality effect varied significantly with sample size and sex.
Serum levels in health and disease
Serum thymosin α1 is significantly lower than in healthy people in hepatitis B, psoriatic arthritis, multiple sclerosis and sepsis, and lower in the sputum of people with cystic fibrosis. The review notes that normal baseline levels and the most effective dose and schedule remain unsettled.
A broad, favourable review
The authors survey its use in immunocompromised states, cancer, vaccine response and sepsis, discuss a possible role in severe COVID-19, and conclude that thymosin α1 deserves further investigation. It is a narrative review and predates the negative TESTS trial.
Impurities in thymalfasin material
Liquid chromatography with high-resolution mass spectrometry separated and quantified 23 thymalfasin-related impurities above 0.1 mg/g in a China Pharmacopoeia standard, then applied the method to three commercial materials. The main impurities included deamidated, aminated and succinimide forms.
What people say, and what was measured
Thymosin alpha-1 has the largest trial record of any peptide sold in the grey market, which makes it the clearest case on this site of evidence pointing in several directions at once. It is approved in other countries and not in the United States, and its biggest trial was negative.
It boosts the immune system, which is why it helps in serious infection.
Heard in: World Journal of Virology, Thymosin alpha 1: A comprehensive review of the literature, which records its use for curbing morbidity and mortality in sepsis and numerous infections (read October 1, 2026). Source
The claim was put to a proper test and failed. In TESTS, a multicentre double-blind placebo-controlled phase 3 trial, 28-day death from sepsis was 23.4% on thymosin alpha-1 and 24.1% on placebo, a hazard ratio of 0.99 (p = 0.93). No secondary or safety outcome differed. Subgroup analyses hinted at differences by age and diabetes, which is a hypothesis, not a result. PMID: 39814420
Tested in people; not shownIt works in COVID by restoring the T cells the virus depletes.
Heard in: World Journal of Virology, Thymosin alpha 1: A comprehensive review of the literature, which discusses the proposal that it could improve outcomes in severely ill COVID-19 patients by preventing excessive T-cell activation (read October 1, 2026). Source
The specific mechanism was measured and did not hold. In COVID-19 patients, CD4 and CD8 counts recovered no better with thymosin alpha-1 than without (286 against 326, and 154 against 170), and virus clearance took longer in the treated group. A separate 49-patient randomised pilot found clinical recovery higher with treatment but not significantly so. PMID: 34149679, 36056913
Tested in people; not shownIt is a proven antiviral treatment for hepatitis B.
Heard in: Grey Peptides listing review, October 1, 2026: listings present thymosin alpha-1 as an antiviral and immune-restoring peptide. Sellers are not named.
This is where the evidence is strongest, and it is older and mixed. In 98 patients with chronic hepatitis B, a 26-week course produced complete virological response in 40.6% against 9.4% of untreated controls at 18 months, with no significant side effects, though the groups looked alike at the end of treatment itself. A later placebo-controlled trial combining it with interferon missed its primary endpoint, with 45.8% against 28.0% HBeAg loss (p = 0.067). PMID: 9581695, 16640105
Tested in people; mixedIt makes vaccines work better.
Heard in: World Journal of Virology, Thymosin alpha 1: A comprehensive review of the literature, which lists use as an enhancer of vaccine response among its applications (read October 1, 2026). Source
Tested in one narrow setting. In haemodialysis patients given an adjuvanted pandemic H1N1 vaccine, both thymosin alpha-1 groups reached higher antibody titres than vaccine alone and met the regulatory criteria, with no adverse events attributed to it. The authors say larger studies in dialysis populations are still needed, and nothing supports the claim in healthy people. PMID: 22178096
Tested in people; supportedEach claim is quoted from where it is said, never from a seller, and checked as of October 1, 2026 against the studies listed below.
Dosing Data
Thymosin α1 is one of the few peptides here with a labelled dose abroad: 1.6 mg under the skin twice a week. Most trials used that dose; the sepsis trial dosed every 12 hours for a week, and one cancer regimen used 2 mg on four days of each cycle.
Educational information, not medical advice. Each dose above is tagged with its source: an approved label, a published human study, animal data, or amounts reported by users. None is a recommendation for you. An unapproved compound has no established safe or effective human dose, and products sold for “research use only” are not made or tested for people. Talk to a doctor before acting on anything on this site, including before you start, stop or change any medicine or dose. Full medical disclaimer.
→ Full Thymosin α1 dosage guide — the labelled Zadaxin regimen, the trial doses, and what the negative sepsis trial means for them.
Side Effects & Contraindications
Reported Side Effects
The controlled trials report reassuring safety, but with few specifics, and the combination cancer trials cannot separate its side effects from the other drugs'.
Contraindications & Cautions
No trial on this page defines contraindications. These cautions follow from its immune effects and from the trial results.
Legal Status
Thymosin α1 is an approved medicine in about 35 countries but not in the US, and US pharmacies cannot compound it. Status as of September 26, 2026.
Frequently Asked Questions
?Does thymosin α1 work for sepsis?
The best evidence says no. TESTS, a double-blind trial of 1,106 adults published in 2025, found 28-day mortality of 23.4% on thymosin α1 and 24.1% on placebo. Earlier small trials had suggested benefits on immune markers and ventilation time, and a 2009 meta-analysis pooled 198 patients, but the large trial did not confirm a survival benefit.
?Is thymosin α1 approved anywhere?
Yes, as Zadaxin (thymalfasin) in about 35 countries, though not the US, mainly for chronic hepatitis B and C, according to our dataset. It is not FDA-approved, and US pharmacies cannot compound it.
?Does it help chronic hepatitis B?
In one 98-patient trial, a 26-week course cleared the virus in 40.6% of patients by 18 months, against 9.4% of untreated patients, but a 52-week course did not beat no treatment significantly. Added to interferon, it produced a non-significant rise in HBeAg loss. These trials predate today's antivirals.
?Did it help in COVID-19?
The evidence conflicts. A 2023 meta-analysis of eight studies found lower mortality, but the studies disagreed sharply with each other. A 275-patient retrospective study found no faster T-cell recovery and slower viral clearance, and a 49-patient pilot trial found faster CD4 recovery without a significant difference in clinical recovery.
?Is thymosin α1 the same as thymosin β4 or TB-500?
No. Both are called thymosins, but they are unrelated in sequence and in what they do: thymosin α1 is an immune regulator, while thymosin β4, and TB-500, a synthetic fragment of it, bind actin and are studied for tissue repair.
?What dose is used?
The Zadaxin label, as recorded in our dataset, uses 1.6 mg under the skin twice a week, and most trials here used that dose. The label has no US approval, and nothing on this page is a recommendation.
References
- [clinical-trial] Wu J, et al. "The efficacy and safety of thymosin α1 for sepsis (TESTS): multicentre, double blinded, randomised, placebo controlled, phase 3 trial." BMJ, 2025;388:e082583. PMID: 39814420.
- [clinical-trial] Chien RN, et al. "Efficacy of thymosin alpha1 in patients with chronic hepatitis B: a randomized, controlled trial." Hepatology, 1998;27(5):1383-7. PMID: 9581695.
- [pubmed] Lim SG, et al. "A randomized, placebo-controlled trial of thymosin-alpha1 and lymphoblastoid interferon for HBeAg-positive chronic hepatitis B." Antivir Ther, 2006;11(2):245-53. PMID: 16640105.
- [pubmed] Sherman KE, et al. "Combination therapy with thymosin alpha1 and interferon for the treatment of chronic hepatitis C infection: a randomized, placebo-controlled double-blind trial." Hepatology, 1998;27(4):1128-35. PMID: 9537454.
- [pubmed] Shehadeh F, et al. "A Pilot Trial of Thymalfasin (Thymosin-α-1) to Treat Hospitalized Patients With Hypoxemia and Lymphocytopenia Due to Coronavirus Disease 2019 Infection." J Infect Dis, 2023;227(2):226-235. PMID: 36056913.
- [pubmed] Wang Z, et al. "Thymosin Alpha-1 Has no Beneficial Effect on Restoring CD4+ and CD8+ T Lymphocyte Counts in COVID-19 Patients." Front Immunol, 2021;12:568789. PMID: 34149679.
- [pubmed] Carraro G, et al. "Thymosin-alpha 1 (Zadaxin) enhances the immunogenicity of an adjuvated pandemic H1N1v influenza vaccine (Focetria) in hemodialyzed patients: a pilot study." Vaccine, 2012;30(6):1170-80. PMID: 22178096.
- [pubmed] Chen C, et al. "Role of thymosin α1 in restoring immune response in immunological nonresponders living with HIV." BMC Infect Dis, 2024;24(1):97. PMID: 38233816.
- [pubmed] Lopez M, et al. "Biochemotherapy with thymosin alpha 1, interleukin-2 and dacarbazine in patients with metastatic melanoma: clinical and immunological effects." Ann Oncol, 1994;5(8):741-6. PMID: 7826907.
- [pubmed] Xu H, et al. "Neoadjuvant immunochemotherapy plus thymalfasin in locally advanced gastric cancer: a prospective clinical trial." BMC Med, 2026;24(1). PMID: 41749205.
- [review] Yu Y, et al. "[Evaluation of efficacy of thymosin alpha1 in the treatment of sepsis: a systematic review]." Zhongguo Wei Zhong Bing Ji Jiu Yi Xue, 2009;21(1):21-4. PMID: 19141185.
- [review] Soeroto AY, et al. "The efficacy of thymosin alpha-1 therapy in moderate to critical COVID-19 patients: a systematic review, meta-analysis, and meta-regression." Inflammopharmacology, 2023;31(6):3317-3325. PMID: 37845598.
- [review] Pica F, et al. "Serum thymosin alpha 1 levels in normal and pathological conditions." Expert Opin Biol Ther, 2018;18(sup1):13-21. PMID: 30063864.
- [review] Dominari A, et al. "Thymosin alpha 1: A comprehensive review of the literature." World J Virol, 2020;9(5):67-78. PMID: 33362999.
- [pubmed] Cheng Y, et al. "Identification and determination of structurally related peptide impurities in thymalfasin by liquid chromatography-high-resolution mass spectrometry." Anal Bioanal Chem, 2022;414(28):8035-8045. PMID: 36207535.
- [fda-pi] Zadaxin (thymalfasin) Prescribing Information. SciClone Pharmaceuticals. (Approved in 35+ countries; not FDA.)
- [pubmed] Garaci E, et al. "Thymosin alpha(1) in combination with cytokines and chemotherapy for the treatment of cancer." Int Immunopharmacol, 2003;3(8):1145-50. PMID: 12860169.
Sources & Citations
Every PMID on this page is PubMed-indexed and has been checked against its record. Two sources in our dataset carry no PMID: the Zadaxin prescribing information and a 2003 cancer review by Garaci and colleagues. Grey Peptides sells nothing and links to no vendor.
Medical Disclaimer: This content is for educational and informational purposes only. It is not medical advice, and nothing here is an instruction to obtain or use any compound. Talk to a licensed clinician about your own situation.