Peptide Briefs

Thymosin Alpha-1: Evidence Grade A | Human Trials, Studies, and Sources

Evidence grade: A. Reviewed October 2026.

Regulatory approval in roughly 30 countries (not the US). At least 12 published randomized controlled trials, including two phase 3 trials in sepsis (one with 1,106 patients, negative), two phase 3 trials in hepatitis C (both negative), one placebo-controlled trial in acute pancreatitis (negative), and a 2026 Cochrane review of 10 hepatitis B trials. Several dozen animal and in-vitro studies.

Also called: thymalfasin, Tα1, Ta1, Zadaxin (brand). Sequence: 28 amino acids, N-terminal acetylated. Ac-Ser-Asp-Ala-Ala-Val-Asp-Thr-Ser-Ser-Glu-Ile-Thr-Thr-Lys-Asp-Leu-Lys-Glu-Lys-Lys-Glu-Val-Val-Glu-Glu-Ala-Glu-Asn-OH. Molecular weight 3,108 Da.

Thymosin alpha-1 is the most-studied peptide on Peptide Briefs and one of the most misread. It has been a licensed drug since the 1990s, it has been in more randomized trials than every other compound in this library combined, and the largest and best-designed of those trials found nothing. That combination is why it grades A and why the grade should not be mistaken for an endorsement. The A measures how much evidence exists and how good it is, not which way it points. Here, much of it points to no effect.

What thymosin alpha-1 is

Thymosin alpha-1 is a 28-amino-acid peptide first isolated from calf thymus in 1977 by Allan Goldstein’s group, who sequenced it from a crude thymic extract called thymosin fraction 5 [1, 2]. The body makes it: it is cleaved from a larger precursor, prothymosin alpha, and circulates at low concentrations. The drug is a synthetic copy of the natural molecule, with an acetyl group on the N-terminus, which is how the natural peptide is also found.

It does not act on a single receptor the way a GLP-1 agonist or a growth hormone secretagogue does. The best-characterized mechanism is signaling through Toll-like receptors on dendritic cells, which pushes them toward a Th1-type response and interleukin-12 production [3]. In practice it is described as an immunomodulator: it raises markers of immune activity (monocyte HLA-DR expression, T-cell counts in some settings) rather than producing a direct effect on a disease process. That distinction matters for reading the trials, because the surrogate markers often move while the clinical outcome does not.

The compound was developed commercially by SciClone Pharmaceuticals under the brand Zadaxin and licensed in Italy, China, and other markets through the 1990s. It was never approved in the United States.

What the studies looked at

1977, discovery. Goldstein and colleagues isolated the peptide from calf thymus and reported its sequence and immunological activity in mice [1]. Two 1979 papers completed the chemistry [2].

1989, influenza vaccine response in elderly men. A double-blind, placebo-controlled trial in 90 men aged 65 to 99 gave thymosin alpha-1 (900 µg/m² subcutaneously twice weekly, eight doses) alongside the seasonal flu vaccine. Antibody response rates were higher with the peptide, with the effect concentrated in the oldest subgroup. No toxicity was seen [4]. This is the origin of the “vaccine adjuvant” use and the design most later adjuvant studies copied.

1998, chronic hepatitis B, Taiwan. Chien and colleagues randomized 98 patients to 26 weeks of treatment (1.6 mg twice weekly), 52 weeks, or no treatment. At 18 months, complete virological response (loss of HBV DNA and HBeAg) was 40.6% with 26 weeks, 26.5% with 52 weeks, and 9.4% untreated. Response rates were similar at the end of treatment and separated only afterward. No responder lost HBsAg [5]. This trial and others like it supported the Zadaxin license in Asia.

1999, chronic hepatitis B, United States. Mutchnick and colleagues ran the US phase 3: 97 HBeAg-positive patients, 1.6 mg twice weekly for 6 months, double-blind, placebo-controlled. Complete response at 12 months was 14% with the peptide versus 4% with placebo, and 25% versus 13% when delayed responders were included. Neither difference reached significance. The authors wrote that the results “do not confirm observations of treatment efficacy reported in other clinical studies” [6]. Same drug, same dose, same disease, different answer from the Taiwan trial.

2004, mechanism. Romani and colleagues showed that the peptide activates dendritic cells through Toll-like receptor and MyD88 signaling, and protects transplanted mice from Aspergillus infection [3]. This paper is the basis for most mechanistic claims made about the compound.

2005 and 2006, hepatitis C, two failed phase 3 trials. SciClone ran two 500-patient phase 3 trials in the US and Europe adding Zadaxin to pegylated interferon in patients who had not responded to prior therapy, one in non-cirrhotic patients and one in early cirrhosis. Both missed the primary endpoint of sustained virological response (NCT00040027, NCT00039962) [7]. These are the trials that ended the US approval effort; the full results were never published in a journal.

2010, metastatic melanoma. A 488-patient randomized phase 2 across five arms tested the peptide at three doses with dacarbazine, with or without interferon. The response-rate endpoint was met in two arms (10 and 12 responses versus 4 in the control arm). Median overall survival was 9.4 versus 6.6 months, hazard ratio 0.80, P = .08, not significant. No added toxicity [8]. The planned phase 3 was never run.

2013, severe sepsis (ETASS). Six Chinese ICUs randomized 361 patients to 1.6 mg twice daily for 5 days then once daily for 2 days, or saline, single-blind. 28-day mortality was 26.0% versus 35.0%, relative risk 0.74 (95% CI 0.54 to 1.02), P = 0.062 on the prespecified test. Monocyte HLA-DR, the immune marker, rose more in the treated group. No drug-related serious adverse events [9]. The authors called the result marginal and designed a larger trial to settle it.

2022, acute necrotizing pancreatitis (TRACE). Sixteen Chinese centers randomized 508 patients with predicted severe disease to 1.6 mg twice daily for 7 days then daily for 7 days, or placebo, double-blind. Infected pancreatic necrosis occurred in 15.7% versus 18.1%, P = 0.48. No difference in organ failure, bleeding, or fistula [10]. A post-hoc analysis found a possible effect in patients with higher baseline lymphocyte counts, which the authors present as hypothesis-generating [11].

2023, COVID-19 prevention in dialysis patients. A 189-patient open-label randomized trial in Kansas City gave the peptide for 8 weeks to hemodialysis patients. COVID-19 infections were 5 versus 7, hospitalizations 27 versus 26, deaths 3 versus 7 (NCT04428008). Posted to ClinicalTrials.gov; the published report is preliminary [12]. A separate US treatment trial in hospitalized COVID-19 patients was terminated after 56 of a planned enrollment (NCT04487444).

2025, sepsis, phase 3 (TESTS). The follow-up to ETASS: 22 centers, 1,106 adults with sepsis, double-blind, placebo-controlled, every 12 hours for up to 7 days. 28-day mortality was 23.4% with the peptide and 24.1% with placebo, hazard ratio 0.97 (95% CI 0.76 to 1.24), P = 0.82. The authors found “no clear evidence” of benefit [13]. This is the largest trial of the compound ever run and it is negative.

2026, Cochrane review, chronic hepatitis B. Ten randomized trials, 1,349 adults. All-cause death 3.0% versus 5.8% across three trials, very low certainty. Serious adverse events 10.1% versus 13.4%, low certainty. No clear difference in HBV-related illness, histology, or well-being. The reviewers rated the evidence very low certainty for every outcome but one, citing small trials, few per outcome, and inconsistent results [14].

What the evidence does not show

  • No benefit in the largest trial ever run. TESTS, 1,106 sepsis patients, double-blind, placebo-controlled: no difference in mortality. The earlier 361-patient single-blind trial that suggested a benefit was superseded by it.
  • No published positive phase 3 outside hepatitis B. Both hepatitis C phase 3 trials failed. The melanoma phase 3 was never run. The pancreatitis trial was negative.
  • Inconsistent hepatitis B results. The Taiwan trial was positive, the US trial was not, and the 2026 Cochrane review rates the whole body of evidence very low certainty.
  • Nothing on the uses it is sold for. There are no controlled human trials of thymosin alpha-1 for “immune support” in healthy people, for chronic fatigue, for Lyme disease, for long COVID, for autoimmune conditions, or for longevity. The compound’s reputation in those areas rests on the mechanism paper and on extrapolation from sick, hospitalized populations.
  • Surrogate markers move, outcomes often don’t. Several trials show higher HLA-DR, T-cell counts, or antibody titers in treated patients alongside no difference in the clinical endpoint. A change in an immune marker is not evidence of a change in health.
  • Dose and duration in sales listings have no trial basis. Trials used 1.6 mg (about 900 µg/m²) subcutaneously, twice weekly for months in hepatitis or twice daily for a week in acute illness. Research-market listings commonly describe other amounts and schedules that have not been studied.
  • No long-term safety data outside the licensed indications. The safety record is good in trials up to 12 months in hepatitis patients and 7 to 14 days in ICU patients. There is no data on years of use in healthy adults.

Regulatory and sport status

  • Licensed abroad, not in the US. Zadaxin (thymalfasin, 1.6 mg per vial, subcutaneous) is approved in roughly 30 countries, including China and Italy, for chronic hepatitis B and, in combination with interferon, chronic hepatitis C [15]. SciClone’s US application effort ended after the two hepatitis C phase 3 failures in 2005 and 2006. It has never been approved by FDA for any use.
  • Not eligible for US compounding. FDA placed thymosin alpha-1 in Category 2 of the interim 503A bulks list in September 2023, meaning it could not be compounded while under review; the nominators withdrew it in September 2024. At the December 4, 2024 Pharmacy Compounding Advisory Committee meeting, FDA recommended against adding either the free base or the acetate to the 503A list, and the committee voted 17 to 4 against each. The majority cited a lack of convincing effectiveness data for the nominated uses [16].
  • WADA. Thymosin alpha-1 is not named on the 2026 Prohibited List. Thymosin beta-4 (TB-500) is. Tested athletes should confirm status with their governing body rather than assume.
  • Research-only sales in the US. Sold as a research chemical, not for human use. The same licensed drug is sold by prescription in the countries that approve it.

Stability, storage, and handling in the laboratory

The licensed product is a lyophilized powder, 1.6 mg per vial, reconstituted with 1.0 mL sterile water immediately before use; the label specifies subcutaneous use only and not intravenous [15]. Lyophilized peptide is stored refrigerated (2 to 8 °C) or frozen for longer storage, protected from light; reconstituted solution is used promptly and not stored. The sequence is acidic (10 of 28 residues are Asp or Glu) and has no cysteine, so disulfide scrambling is not a concern, but the N-terminal acetyl group is a feature a certificate of analysis should confirm: an unacetylated 28-mer is a different molecule with a mass 42 Da lower. Expected monoisotopic mass for the acetylated peptide is about 3,106 Da; average molecular weight is 3,108.3 Da. A certificate should show identity by mass spectrometry against that value, purity by HPLC, and a lot number that matches the vial.

Common questions

Is thymosin alpha-1 FDA approved?

No. It has never been approved in the United States for any use. It is approved in about 30 other countries under the brand name Zadaxin, mainly for chronic hepatitis B. In December 2024, an FDA advisory committee voted 17 to 4 against allowing US pharmacies to compound it.

Is thymosin alpha-1 the same as TB-500?

No. TB-500 is a fragment of thymosin beta-4, a different protein with a different sequence and a different proposed role (cell migration and tissue repair). Thymosin alpha-1 is a 28-amino-acid immune-signaling peptide. They share the word “thymosin” because both were first isolated from thymus extract in the 1970s, and nothing else. TB-500 is on the WADA Prohibited List; thymosin alpha-1 is not named on it. See the TB-500 page.

If it’s an approved drug, why does the evidence look so weak?

Because the approvals rest on hepatitis B trials from the 1990s that later trials and the 2026 Cochrane review could not confirm with any confidence. Approval in one country at one time is a fact about the regulator’s standard then, not a permanent verdict on the drug. The grade key treats approval anywhere as an A because it means a full human safety and efficacy package exists; it does not mean the efficacy package was convincing.

Why does a compound with a negative 1,106-patient trial grade higher than BPC-157?

The grade measures the amount and quality of evidence, not the direction. BPC-157 has no controlled human trial at all, so no one can say whether it works. Thymosin alpha-1 has been tested properly, and in sepsis the answer was no. A clear negative answer is more evidence than no answer.

Is it safe?

In trials up to 12 months, adverse events were no more frequent than placebo, and in several trials less frequent. That record covers sick, monitored patients at the licensed dose. It says nothing about long-term use in healthy people, and nothing about product sold outside the licensed supply chain, where identity and purity are whatever the certificate for your specific lot says.

Does it “boost the immune system”?

It raises some immune markers in some populations. Whether that translates to fewer infections or better outcomes is what the trials tested, and in the largest ones the answer was no. “Boosts the immune system” is a description of a lab value, not of a health result.

What would change the grade?

Nothing would move it up; A is the ceiling. It would stay A regardless of further negative trials, because the grade reflects the existence of the evidence base. What would change is the text of this page, which is updated as trials report. The next scheduled readout is the TESTS subgroup analyses and any phase 3 in oncology adjunct use.

Sources

  1. Goldstein AL, Low TL, McAdoo M, et al. Thymosin alpha1: isolation and sequence analysis of an immunologically active thymic polypeptide. Proc Natl Acad Sci U S A. 1977;74(2):725-729. PMID 265536
  2. Low TL, Goldstein AL. The chemistry and biology of thymosin. II. Amino acid sequence analysis of thymosin alpha1 and polypeptide beta1. J Biol Chem. 1979;254(3):987-995. PMID 762108
  3. Romani L, Bistoni F, Gaziano R, et al. Thymosin alpha 1 activates dendritic cells for antifungal Th1 resistance through toll-like receptor signaling. Blood. 2004;103(11):4232-4239. PMID 14982877
  4. Gravenstein S, Duthie EH, Miller BA, et al. Augmentation of influenza antibody response in elderly men by thymosin alpha one. A double-blind placebo-controlled clinical study. J Am Geriatr Soc. 1989;37(1):1-8. PMID 2642497
  5. Chien RN, Liaw YF, Chen TC, Yeh CT, Sheen IS. Efficacy of thymosin alpha1 in patients with chronic hepatitis B: a randomized, controlled trial. Hepatology. 1998;27(5):1383-1387. PMID 9581695
  6. Mutchnick MG, Lindsay KL, Schiff ER, et al. Thymosin alpha1 treatment of chronic hepatitis B: results of a phase III multicentre, randomized, double-blind and placebo-controlled study. J Viral Hepat. 1999;6(5):397-403. PMID 10607256
  7. SciClone Pharmaceuticals. Phase 3 hepatitis C trial results, press releases of December 13, 2005 and May 2006 (NCT00040027; NCT00039962). No peer-reviewed publication of the primary results. ClinicalTrials.gov NCT00040027
  8. Maio M, Mackiewicz A, Testori A, et al. Large randomized study of thymosin alpha 1, interferon alfa, or both in combination with dacarbazine in patients with metastatic melanoma. J Clin Oncol. 2010;28(10):1780-1787. PMID 20194853
  9. Wu J, Zhou L, Liu J, et al. The efficacy of thymosin alpha 1 for severe sepsis (ETASS): a multicenter, single-blind, randomized and controlled trial. Crit Care. 2013;17(1):R8. PMID 23327199
  10. Ke L, Zhou J, Mao W, et al. Immune enhancement in patients with predicted severe acute necrotising pancreatitis: a multicentre double-blind randomised controlled trial. Intensive Care Med. 2022;48(7):899-909. PMID 35713670
  11. Ke L, Mao W, Shao F, et al. Association between pretreatment lymphocyte count and efficacy of immune-enhancing therapy in acute necrotising pancreatitis: a post-hoc analysis of the TRACE trial. EClinicalMedicine. 2023;58:101915. PMID 37007743
  12. Tuthill CW, Awad A, Parrigon M, Ershler WB. A pilot trial of thymalfasin (Ta1) to prevent covid-19 infection and morbidities in renal dialysis patients: preliminary report. Int Immunopharmacol. 2023;117:109950. PMID 36881981. Results posted at ClinicalTrials.gov NCT04428008.
  13. Wu J, Pei F, Zhou L, et al; TESTS study collaborator group. 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
  14. Naing C, Ni H, Aung HH, et al. Thymosin-α1 for people with chronic hepatitis B. Cochrane Database Syst Rev. 2026;9:CD014610. PMID 42713852
  15. Health Sciences Authority Singapore. Zadaxin Injection product information, SIN07483P (thymosin alpha 1, 1.6 mg/vial; registrant SciClone Pharmaceuticals International). ndf.gov.sg
  16. US Food and Drug Administration. Final Summary Minutes, Pharmacy Compounding Advisory Committee Meeting, December 4, 2024 (thymosin alpha-1 and thymosin alpha-1 acetate; votes 4 yes, 17 no). Approved February 21, 2025. fda.gov