{"id":"thymosin-alpha-1","name":"Thymosin α1","aliases":["thymalfasin","Zadaxin","Tα1","thymosin alpha 1"],"url":"https://lyoresearch.com/compounds/thymosin-alpha-1","summary":"Thymosin α1 is a 28-amino-acid peptide from the thymus that nudges T-cells and dendritic cells toward a stronger antiviral response. It has been sold as Zadaxin for hepatitis B and as an immune adjunct in China, Italy and some thirty other countries since the 1990s, but the largest trial ever run on it — 1,106 adults with sepsis, published in the BMJ in January 2025 — found no reduction in 28-day mortality (23.4% versus 24.1%). It is not approved in the US, EU-wide or UK.","overall_grade":"B","overall_grade_meaning":"probable, not settled","human_trials":"20+ RCTs","regulatory_status":"Approved outside US/EU (Zadaxin)","outcomes":[{"outcome":"Sepsis mortality","grade":"A","grade_meaning":"established in humans","effect_size":"not measurable","adverse":false,"human_studies":"1 large phase 3 RCT + earlier smaller RCTs","evidence":"TESTS, 1,106 adults in 22 Chinese ICUs, twice-daily injections for 7 days: 28-day mortality 23.4% versus 24.1% on placebo (hazard ratio 0.97, 95% CI 0.76–1.24). No secondary or safety outcome differed. Earlier smaller trials that suggested benefit are superseded.","references":[{"citation":"Liu F, et al. The efficacy and safety of thymosin α1 for sepsis (TESTS): multicentre, double blinded, randomised, placebo controlled, phase 3 trial.","where":"BMJ, 2025; 388:e082583","url":"https://pubmed.ncbi.nlm.nih.gov/39814420/"}]},{"outcome":"Chronic hepatitis B (viral response)","grade":"B","grade_meaning":"probable, not settled","effect_size":"small","adverse":false,"human_studies":"10+ RCTs, mostly small","evidence":"Trials from the 1990s–2000s show modest increases in sustained response, alone or with interferon; heterogeneous quality. The basis for the Zadaxin approvals.","references":[{"citation":"Thymalfasin (Zadaxin) clinical overview: hepatitis B and vaccine-adjuvant randomised trials.","where":"Multiple journals, 1996–2015","url":"https://pubmed.ncbi.nlm.nih.gov/?term=thymalfasin+randomized+hepatitis+B"}]},{"outcome":"Vaccine response in the elderly and dialysis patients","grade":"B","grade_meaning":"probable, not settled","effect_size":"small","adverse":false,"human_studies":"Several RCTs","evidence":"Improved seroconversion to influenza and hepatitis B vaccines in older adults and haemodialysis patients in randomised studies; effect sizes moderate, trials small.","references":[{"citation":"Thymalfasin (Zadaxin) clinical overview: hepatitis B and vaccine-adjuvant randomised trials.","where":"Multiple journals, 1996–2015","url":"https://pubmed.ncbi.nlm.nih.gov/?term=thymalfasin+randomized+hepatitis+B"}]},{"outcome":"COVID-19 outcomes","grade":"C","grade_meaning":"weak human evidence","effect_size":"small","adverse":false,"human_studies":"Observational + small RCTs","evidence":"Chinese observational cohorts and small randomised studies reported lower mortality in severe COVID-19; confounded and never confirmed in a large trial.","references":[{"citation":"Efficacy of thymosin α1 for sepsis: a systematic review and meta-analysis of randomized controlled trials.","where":"Front Cell Infect Microbiol, 2025","url":"https://www.frontiersin.org/journals/cellular-and-infection-microbiology/articles/10.3389/fcimb.2025.1673959/full"}]},{"outcome":"Safety","grade":"A","grade_meaning":"established in humans","effect_size":"not measurable","adverse":true,"human_studies":"TESTS + decades of use","evidence":"Injection-site reactions; no signal for serious harm in TESTS or in long clinical use. Subgroup findings in TESTS (worse in under-60s, better in diabetics) are hypothesis-generating only.","references":[{"citation":"Liu F, et al. The efficacy and safety of thymosin α1 for sepsis (TESTS): multicentre, double blinded, randomised, placebo controlled, phase 3 trial.","where":"BMJ, 2025; 388:e082583","url":"https://pubmed.ncbi.nlm.nih.gov/39814420/"}]}],"regions":[{"region":"European Union","status":"Authorised in Italy only","note":"Zadaxin is nationally authorised in Italy; no EU-wide marketing authorisation. Elsewhere in the EU it is an unauthorised medicine."},{"region":"United States","status":"Not approved; compounding withdrawn","note":"Orphan designations but no approval. Its 503A compounding nomination is listed as withdrawn (April 2026)."},{"region":"United Kingdom","status":"Not licensed","note":"No MHRA licence; unlicensed medicine when supplied for human use."},{"region":"Australia","status":"Not registered","note":"Not on the ARTG; prescription-only substance."},{"region":"Canada","status":"Not authorised","note":"No DIN."},{"region":"Sport (WADA)","status":"Not on the list","note":"Approved in several countries, so S0 does not apply; not named in any section."}],"faq":[{"q":"Is thymosin alpha 1 approved?","a":"In China, Italy and roughly thirty other countries, yes, as Zadaxin for hepatitis B and as an immune adjunct. Not in the US, not EU-wide, not in the UK, Australia or Canada."},{"q":"Does thymosin alpha 1 help in sepsis?","a":"The best evidence says no. TESTS, a 1,106-person double-blind phase 3 trial published in the BMJ in 2025, found 28-day mortality of 23.4% with the drug and 24.1% with placebo. Earlier meta-analyses suggesting benefit rested on smaller trials."},{"q":"Is it the same as TB-500?","a":"No. Thymosin α1 and thymosin β4 are different peptides with different biology. TB-500 is a fragment of thymosin β4, has no approvals anywhere, and is prohibited in sport; thymosin α1 is an approved immune drug in several countries and not on the WADA list."}],"references":[{"cite":"Liu F, et al. The efficacy and safety of thymosin α1 for sepsis (TESTS): multicentre, double blinded, randomised, placebo controlled, phase 3 trial.","where":"BMJ, 2025; 388:e082583","url":"https://pubmed.ncbi.nlm.nih.gov/39814420/","note":"1,106 adults; 28-day mortality 23.4% vs 24.1%."},{"cite":"Thymalfasin (Zadaxin) clinical overview: hepatitis B and vaccine-adjuvant randomised trials.","where":"Multiple journals, 1996–2015","url":"https://pubmed.ncbi.nlm.nih.gov/?term=thymalfasin+randomized+hepatitis+B","note":"Heterogeneous, mostly small RCTs."},{"cite":"Efficacy of thymosin α1 for sepsis: a systematic review and meta-analysis of randomized controlled trials.","where":"Front Cell Infect Microbiol, 2025","url":"https://www.frontiersin.org/journals/cellular-and-infection-microbiology/articles/10.3389/fcimb.2025.1673959/full","note":"Includes TESTS; earlier pooled estimates were driven by small trials."}],"last_reviewed":"2026-09-03","literature_searched_to":"2026-09-03","changelog":[{"date":"2026-09-03","note":"Initial publication, led by the TESTS trial."}],"license":"CC BY 4.0 — cite as “LYO Research” with a link.","methodology":"https://lyoresearch.com/methodology"}