Thymosin alpha-1: what has been measured about safety

Thymosin alpha-1 has the deepest safety record of any unapproved compound on this site, and the anchor is a single trial. A 2025 phase 3 published in the BMJ randomised 1,106 adults with sepsis across 22 centres, masked from participants, carers, investigators and outcome assessors alike, and reports that no secondary or safety outcome differed statistically significantly between the treated group and placebo [1].

That is the most useful safety observation on this page and its boundaries are part of it. It measured critically ill adults in intensive care over a treatment period, in a trial whose primary outcome was mortality rather than harm, and it is a statement about what that study measured in that population rather than a general statement about the compound.

Two further records sit beside it and point in a different direction. FDA lists the molecule among bulk substances that may present significant safety risks for compounding, citing immunogenicity by certain routes and complexities of peptide-related impurities and characterisation, and stating that the safety-related information available is inadequate for the agency to understand the extent of any safety issues raised [25]. And an independent 2022 analytical study identified and quantified 23 related impurities above 0.1 mg per gram in a pharmacopoeial reference standard for this molecule [16].

What this page reports, and what it does not

We report what has been documented. We do not prescribe what should be done.

Every sentence below reports what a named source measured, stated or searched, in what population, and what it found. Where a source's own limitation travels with its result, that limitation is reported in the same paragraph rather than left for a reader to find.

This page publishes no dose, no schedule, no route instruction and no list of people who should avoid anything. A list of who should not use a compound is a directions-for-use document, and it only makes sense if the reader is going to use the thing. What replaces it is a description of the compound and its record, written about the molecule rather than about the reader.

One thing about this compound's position needs stating before the first section. It is registered as a medicine outside the United States and it has no approved application inside it, and both are true at once [24]. So the safety record here is a mix of trial evidence, an agency statement about compounding, and an analytical literature, and those three kinds of document answer different questions.

What has been measured

What the largest trial reported, and over what

The 2025 phase 3 trial randomised 1,106 adults with sepsis across 22 centres against placebo, with masking extending to participants, carers, investigators and outcome assessors. Its published report states that no secondary or safety outcome differed statistically significantly between the two groups [1].

This is the single most informative safety observation on the page, and the reason is design rather than result. A quadruple-masked placebo-controlled trial at that enrolment is the arrangement most capable of detecting a difference in either direction, and a trial that finds none has produced information rather than an absence of it. That is a different situation from every compound in this catalogue whose surveillance databases are empty because nobody reports into them.

What it covers is also specific. The population was critically ill adults in intensive care, the exposure ran across a treatment period rather than years, and the trial was built around 28-day mortality. A safety finding from that trial is a finding about that population over that period, and it does not describe an otherwise healthy adult taking the compound for months. [Human RCT] [1]

What FDA said, and what kind of statement it is

FDA lists this molecule among bulk drug substances for use in compounding that may present significant safety risks. Its stated reasoning, read from that page on 23 August 2026, is that compounded drugs containing it may pose significant risk for immunogenicity for certain routes of administration and may have complexities with regard to peptide-related impurities and characterisation of the active ingredient, and that the safety-related information is inadequate for the agency to sufficiently understand the extent of any safety issues raised [25].

Read that sentence carefully, because it is a statement about missing information rather than a finding of harm. The agency is not reporting that the substance injured anyone. It is reporting that it cannot judge, and naming the two properties it cannot judge.

The impurity half, which has a measurement behind it

One of the two properties the agency names has been measured independently, which is unusual for anything on this list. A 2022 study applied high-resolution mass spectrometry to a pharmacopoeial reference standard for this molecule and to three commercial materials, and identified and quantified 23 related impurities above 0.1 mg per gram in the standard itself, across classes including deamination, amination, succinimide formation, amino acid insertion and deletion, dimers and isomers [16].

More than half of them arise directly or indirectly from the asparagine residue at one end of the sequence, which makes the impurity profile a property of the molecule rather than of any particular manufacturer [16]. That is what an analysis of this compound has to be capable of separating, and it is the reason a bare purity percentage answers less here than it appears to. [In-vitro] [16]

What the rest of the trial literature reports

The 2013 trial in 361 patients with severe sepsis records no serious drug-related adverse event [2]. A COVID-19 treatment pilot records nine serious adverse events among treated patients, all judged by the investigators not to be related to the drug [6].

Both observations come with the same qualification, and it is a structural one rather than a criticism. Each enrolled people who were already seriously ill, which makes a serious event during the study period common regardless of what was given, and attribution in that setting is an investigator's judgement rather than a measurement. The 2025 trial's masking is what makes its version of the same question worth more than either.

The wider registered programme adds little to this. 62 registrations name this molecule in their interventions, 9 of them at phase 3, and only 2 of the 62 have posted results [23]. Two 500-participant phase 3 trials in hepatitis C started in 2002, completed, and no results or publication for either was located [20]. Whatever those studies observed is not on the public record. [Human RCT] [2] [6]

The reviews that call the profile excellent, and who wrote them

A 2015 review describes the safety profile of this molecule as excellent and virtually devoid of toxicity [15], and a 2024 review covers its safety and efficacy across human clinical trials [12]. Both are cited here as stated assessments rather than as independent findings.

The reason for that framing is on the face of the first one: it is written by authors reviewing a field they work in. That is ordinary in a specialist literature and it is also the thing a reader needs to know before weighing a summary sentence against a trial result.

This site does not describe any compound as safe. What is on the record is what the studies measured, over the periods they measured it, in the populations they enrolled, and the 2025 trial is the strongest instance of that on this page rather than any review's summary of the field. [Anecdote] [15] [12]

What has not been characterised

Set out plainly, so the shape of the gap is visible rather than implied. Every trial on this record enrolled people with a specific illness: sepsis, hepatitis, cancer, COVID-19, pancreatitis or chronic obstructive pulmonary disease. No trial located for this page enrolled an otherwise healthy adult taking the compound for general immune support, which is what it is sold for, so nothing in the record describes that use or that population.

Duration is the second gap. The trials that report safety observations ran over treatment periods measured in days and weeks, and the 2025 trial's treatment course was one of them [1]. Nothing published follows anyone taking this molecule over years.

And 60 of the 62 registrations have posted nothing [23]. What those studies observed is unknown rather than negative, and the two words are not interchangeable. A trial count for this compound is a count of filings unless the posted-results count travels with it.

One further boundary, because the names invite it. Nothing on this page describes thymosin beta-4, which is a different molecule doing a different job and separated out of the same bovine thymus extract that this compound came from [14]. Its record is thinner and shaped differently, and what it holds is set out on the thymosin beta-4 safety record, linked under Safety records this page refers to at the foot of this page.

Our takeTwo sentences about this compound get quoted one at a time and in opposite directions. The 2025 trial found no safety outcome differing from placebo across 1,106 masked participants, which is a real measurement rather than an empty database, and it measured critically ill adults over a treatment course. FDA's compounding entry says it lacks the information to judge the risks and names immunogenicity and impurity characterisation as what it cannot judge, which is not a finding of harm. Neither sentence is the whole record, and the compound is one of very few here where reading both is actually possible.

Talk to a licensed clinician about anything concerning your health.

Frequently asked questions

References

1. Wu J, Pei F, Zhou L, Li W, Sun R, Li Y, Wang Z, He Z, Zhang X, Jin X, Long Y, Cui W, Wang C, Chen E, Zeng J, Yan J, Lin Q, Zhou F, Huang L, Shang Y, Duan M, Zheng W, Zhu D, Kou Q, Zhang S, Liu Y, Yao C, Shang M, Peng S, Zhou Q, Cheng KK, Guan X, 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. PMID 39814420 DOI 10.1136/bmj-2024-082583
2. Wu J, Zhou L, Liu J, Ma G, Kou Q, He Z, Chen J, Ou-Yang B, Chen M, Li Y, Wu X, Gu B, Chen L, Zou Z, Qiang X, Chen Y, Lin A, Zhang G, Guan X. The efficacy of thymosin alpha 1 for severe sepsis (ETASS): a multicenter, single-blind, randomized and controlled trial. Crit Care. 2013. PMID 23327199 DOI 10.1186/cc11932
3. Ciancio A, Andreone P, Kaiser S, Mangia A, Milella M, Solà R, Pol S, Tsianos E, De Rosa A, Camerini R, McBeath R, Rizzetto M. Thymosin alpha-1 with peginterferon alfa-2a/ribavirin for chronic hepatitis C not responsive to IFN/ribavirin: an adjuvant role? J Viral Hepat. 2012. PMID 22233415 DOI 10.1111/j.1365-2893.2011.01524.x
4. Yang YF, Zhao W, Zhong YD, Yang YJ, Shen L, Zhang N, Huang P. Comparison of the efficacy of thymosin alpha-1 and interferon alpha in the treatment of chronic hepatitis B: a meta-analysis. Antiviral Res. 2008. PMID 18078676 DOI 10.1016/j.antiviral.2007.10.014
5. Chien RN, Liaw YF. Thymalfasin for the treatment of chronic hepatitis B. Expert Rev Anti Infect Ther. 2004. PMID 15482167 DOI 10.1586/14787210.2.1.9
6. Shehadeh F, Benitez G, Mylona EK, Tran QL, Tsikala-Vafea M, Atalla E, Kaczynski M, Mylonakis E. 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. PMID 36056913 DOI 10.1093/infdis/jiac362
7. 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. PMID 36881981 DOI 10.1016/j.intimp.2023.109950
8. Soeroto AY, Suryadinata H, Yanto TA, Hariyanto TI. The efficacy of thymosin alpha-1 therapy in moderate to critical COVID-19 patients: a systematic review, meta-analysis, and meta-regression. Inflammopharmacology. 2023. PMID 37845598 DOI 10.1007/s10787-023-01354-2
9. Cao A, Feng F, Zhou X. Thymosin Alpha 1 Plus Routine Treatment for the Acute Exacerbation of Chronic Obstructive Pulmonary Disease: A Systematic Review and Meta-Analysis. J Coll Physicians Surg Pak. 2024. PMID 39648386 DOI 10.29271/jcpsp.2024.12.1497
10. Tian Y, Yao J, Ma Y, Zhang P, Zhou X, Xie W, Tang W. Thymosin alpha 1 alleviates inflammation and prevents infection in patients with severe acute pancreatitis through immune regulation: a systematic review and meta-analysis. Front Immunol. 2025. PMID 40599771 DOI 10.3389/fimmu.2025.1571456
11. Simonova MA, Ivanov I, Shoshina NS, Komyakova AM, Makarov DA, Baranovskii DS, Klabukov ID, Telepenina KP, Atiakshin DA, Shegay PV, Kaprin AD, Stepanenko VN. Aging and Thymosin Alpha-1. Int J Mol Sci. 2025. PMID 41373628 DOI 10.3390/ijms262311470
12. Dinetz E, Lee E. Comprehensive Review of the Safety and Efficacy of Thymosin Alpha 1 in Human Clinical Trials. Altern Ther Health Med. 2024. PMID 38308608
13. Ancell CD, Phipps J, Young L. Thymosin alpha-1. Am J Health Syst Pharm. 2001. PMID 11381492 DOI 10.1093/ajhp/58.10.886
14. Camerini R, Garaci E. Historical review of thymosin α 1 in infectious diseases. Expert Opin Biol Ther. 2015. PMID 26098768 DOI 10.1517/14712598.2015.1033393
15. Tuthill C, Rios I, McBeath R. Thymosin alpha 1: past clinical experience and future promise. Ann N Y Acad Sci. 2010. PMID 20536460 DOI 10.1111/j.1749-6632.2010.05482.x
16. Cheng Y, Wu P, Kan Y, Li M, Li H. Identification and determination of structurally related peptide impurities in thymalfasin by liquid chromatography-high-resolution mass spectrometry. Anal Bioanal Chem. 2022. PMID 36207535 DOI 10.1007/s00216-022-04336-5
17. ClinicalTrials.gov. NCT02867267, the TESTS trial: a phase 3 multicentre randomized quadruple-masked placebo-controlled trial of thymosin alpha 1 in 1,106 adults with sepsis, sponsored by Sun Yat-sen University with SciClone Pharmaceuticals as collaborator, running September 2016 to March 2021, primary outcome 28-day all-cause mortality. No results are posted to the registry; the trial is published. Read through the v2 API on 23 August 2026. ClinicalTrials.gov. 2026. NCT02867267
18. ClinicalTrials.gov. NCT00711620, the ETASS trial: a multicentre randomized controlled trial of thymosin alpha 1 in 361 patients with severe sepsis, sponsored by Sun Yat-sen University, completed. The registry records masking as DOUBLE, naming participant and outcomes assessor, while the publication's title describes the trial as single-blind. Both are recorded here and neither is resolved. Read through the v2 API on 23 August 2026. ClinicalTrials.gov. 2026. NCT00711620
19. ClinicalTrials.gov. NCT01178996, a phase 3 multicentre double-masked trial in 552 patients with chronic hepatitis C who did not respond to prior peginterferon and ribavirin, sponsored by sigma-tau i.f.r. S.p.A. with SciClone Pharmaceuticals as collaborator, completed July 2009, primary outcome sustained virological response at week 72. No results are posted to the registry; the trial is published. Read through the v2 API on 23 August 2026. ClinicalTrials.gov. 2026. NCT01178996
20. ClinicalTrials.gov. NCT00039962 and NCT00040027, two phase 3 randomized double-masked trials of thymalfasin plus peginterferon alfa-2a in hepatitis C non-responders, 500 participants each, sponsored by SciClone Pharmaceuticals, both started in 2002 and both recorded as completed. Neither has results posted, and no publication was located for either. Read through the v2 API on 23 August 2026. ClinicalTrials.gov. 2026. NCT00039962
21. ClinicalTrials.gov. NCT00911443, a phase 2 open randomized dose-ranging trial in 488 participants with malignant melanoma, sponsored by sigma-tau i.f.r. S.p.A., completed September 2007, five arms of 97 to 99. Posted results: overall tumour response (complete plus partial) 7, 10, 6 and 12 in the four thymosin-alpha-1 arms against 4 in the dacarbazine plus interferon control arm; median overall survival 9.3, 8.6, 10.3 and 9.3 months against 6.6; median progression-free survival 1.9, 1.8, 1.8 and 2.0 months against 1.8. No statistical analyses are posted for any outcome. Read through the v2 API on 23 August 2026. ClinicalTrials.gov. 2026. NCT00911443
22. ClinicalTrials.gov. NCT04428008, a randomized open-label trial of thymalfasin to prevent COVID-19 in 189 renal dialysis patients, completed January 2023. Posted results: COVID-19 infection in 5 of 91 on treatment against 7 of 98 in the control arm; hospitalisation 27 against 26; non-COVID infections 8 against 6; deaths 3 against 7. No analyses are posted. The record's limitations field states that the introduction of vaccine during the study made detection of infection by seroconversion unreliable. Read through the v2 API on 23 August 2026. ClinicalTrials.gov. 2026. NCT04428008
23. ClinicalTrials.gov. Registry sweep for thymalfasin, thymosin alpha 1, thymosin alpha-1, Zadaxin and the bare term thymosin, run through the v2 API on 23 August 2026. The five queries return 91 distinct records, of which 62 name thymosin alpha-1 in their interventions: 9 at phase 3 including one phase 2/3, 32 at phase 2 including phase 1/2 and 2/3, 7 at phase 4, and 2 observational. Two of the 62 have posted results. The remaining 29 records in the union are almost entirely thymosin beta-4, a different molecule covered separately on this site. ClinicalTrials.gov. 2026. ClinicalTrials.gov
24. US Food and Drug Administration. Drugs@FDA approved drug products, queried through the openFDA drugsfda endpoint on 23 August 2026 for thymalfasin, thymosin and Zadaxin across the generic name and brand name fields. All three queries returned NOT_FOUND: there is no approved US application under any of these names. openFDA. 2026. openFDA drugsfda
25. US Food and Drug Administration. Certain Bulk Drug Substances for Use in Compounding that May Present Significant Safety Risks. The category 2 table carries the row Thymosin-alpha 1 (Ta1), with the stated reasoning that compounded drugs containing it may pose significant risk for immunogenicity for certain routes of administration and may have complexities with regard to peptide-related impurities and API characterization, and that the safety-related information is inadequate for the agency to sufficiently understand the extent of any safety issues raised. Page content current as of 22 April 2026, fetched with a browser user agent and read on 23 August 2026. FDA human drug compounding. 2026. FDA category 2 list
26. World Anti-Doping Agency. The 2026 Prohibited List. Cited here only for the definition of class S0, which covers substances with no current approval by any governmental regulatory health authority for human therapeutic use. Thymosin alpha-1 holds approvals as a medicine outside the United States, so that definition appears not to reach it. This site did not establish whether any other class on the list names or reaches this compound, and states the placement as unsettled rather than resolved. The URL serves zero bytes to automation and is ledgered in tools/unverified-sources.json. World Anti-Doping Agency. 2026. WADA 2026 Prohibited List